1. Supported by Eli Lilly and Company. Eli Lilly and Company has not influenced the content of this publication Developed in association with the European Thoracic Oncology Platform 6–9 September 2015 | Denver, Colorado, USA 16th World Conference on Lung Cancer (WCLC)

2. Letter from Prof Rolf Stahel Dear Colleagues It is my pleasure to present this ETOP slide set which has been designed to highlight and summarise key findings in thoracic cancers from the major congresses in 2015. This slide set specifically focuses on the IASLC 16 th World Conference on Lung Cancer and is available in 4 languages – English, French, Italian and Japanese. The area of clinical research in oncology is a challenging and ever changing environment. Within this environment we all value access to scientific data and research which helps to educate and inspire further advancements in our roles as scientists, clinicians and educators. I hope you find this review of the latest developments in thoracic cancers of benefit to you in your practice. If you would like to share your thoughts with us we would welcome your comments. Please send any correspondence to etop@etop.eu-org.etop@etop.eu-org I would like to thank our ETOP members Drs Solange Peters and Martin Reck for their roles as Editors – for prioritising abstracts and reviewing slide content – also Dr Serena Ricciardi for overseeing translation to Italian. The slide set you see before you would not be possible without their commitment and hard work. And finally, we are also very grateful to Lilly Oncology for their financial, administerial and logistical support in the realisation of this complex yet rewarding activity. Yours sincerely, Rolf Stahel President, ETOP Foundation Council

3. ETOP Medical Oncology Slide Deck Editors 2015 Focus: Advanced NSCLC (not radically treatable stage III & stage IV) and related biomarker data Dr Solange Peters Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland Focus: Advanced NSCLC (not radically treatable stage III & stage IV) and related biomarker data Dr Solange Peters Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland Focus: Early and locally advanced NSCLC (stage I–III) and related biomarker data / other malignancies Dr Martin Reck Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany Focus: Early and locally advanced NSCLC (stage I–III) and related biomarker data / other malignancies Dr Martin Reck Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany

4. Contents Biomarkers and screening Early stage and locally advanced NSCLC – Stages I, II and III Advanced NSCLC – Not radically treatable stage III and stage IV –1 st line –Later lines Other malignancies –SCLC and mesothelioma –Rare tumours –Brain metastases

5. Biomarkers and screening

6. ORAL06.03: Genome-Wide Gene Copy Number Analysis by OncoScan TM FFPE Assay in 976 Resected NSCLC From LACE-Bio2 – Tsao M et al Study objectives –To identify novel prognostic/predictive markers using genome-wide copy number profiling and to investigate the associations between copy number aberrations and survival using the LACE-Bio bio-bank Study design –DNA was extracted from FFPE tumour samples (n=1,013) and profiled using Affymetrix OncoScanTM arrays with >300,000 probes (primary analysis n=976) Key results –OS, DFS & LCSS were similar in patients with/without gene copy number alterations –195 aberrant MCRs were significantly different between ADC and SCC More gains in SCC in 3q, 22q and 12; more losses in SCC in 3p, 4, 5q Conclusions –Chromosomal MCRs were identified that harbour candidate copy number aberrant genes in patients with NSCLC –Strong copy number differences were observed between ADC and SCC and, therefore, copy number aberrations may be histology specific Tsao et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL06.03 FFPE, formalin-fixed paraffin embedded; LCSS, lung cancer specific survival; MCR, minimum common region

7. ORAL09.02: Results of the Fourth Screening Round of the NELSON Lung Cancer Screening Study – Yousaf-Khan U et al Study objective To investigate whether low-dose CT screening of patients at high-risk of developing lung cancer would reduce lung cancer mortality by ≥25% vs. no screening Four rounds (R) of low-dose multi-slice computer tomography scanning: –R1 at baseline; R2 at 1 year, R2 at 3 years and R4 at 5.5 years The current analysis assessed mortality at 10 years after randomisation Yousaf-Khan et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL09.02 R PD Key patient inclusion criteria Age 50–75 years Current/former smokers (smoking history ≥15 cigarettes/day for 25 years or ≥10 cigarettes/day for 30 years) (n=15,822) Control arm (n=7,907) Screen arm (n=7,915)

8. ORAL09.02: Results of the Fourth Screening Round of the NELSON Lung Cancer Screening Study – Yousaf-Khan U et al Key results –More patients shifted to a higher stage of lung cancer at R4 vs. R1–3 (p<0.001) Conclusion –A 2.5-year interval between R3 and R4 appears to be too long Unfavourable stage distribution shift More aggressive types of screen-detected lung cancer Yousaf-Khan et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL09.02 Screen results, %NegativeIndeterminatePositive R1–387.210.82.0 R496.02.0 R1–R3 HistologyR4 Histology p=0.055

9. ORAL09.03: The Danish Lung Cancer Screening Trial: Results 5 Years after Last CT Screening – Pedersen JH et al Study objective To investigate the effect of computed tomography (CT) screening on mortality, causes of death, lung cancer findings and risk stratification in patients followed up for 5 years since last CT screening Pedersen et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL09.03 R PD Key patient inclusion criteria Smokers/ex-smokers Aged 50–70 years ≥20 pack years FEV 1 ≥30% predicted (n=4,104) Control 5 annual visits (n=2,052) CT screening 5 annual low-dose CTs (n=2,052)

10. ORAL09.03: The Danish Lung Cancer Screening Trial: Results 5 Years after Last CT Screening – Pedersen JH et al Pedersen et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL09.03 Key results –Significantly more lung cancer cases were seen in the screening vs. control group –In total there were 165 deaths in the CT group and 163 in the control group, of which 39 and 38, respectively, were lung cancer deaths –Lung cancer death risk increased with age: HR 2.4 (95%CI 1.5, 3.9); p<0.001 Conclusions –CT screening of current or ex-smokers aged ≥50 years with a smoking history of ≥20 pack-years did not reduce lung cancer mortality –Focusing on high-risk patients based on age, amount of smoking and COPD, may improve screening outcomes –13% of lung cancer mortality occurred in low- risk patients (without COPD, <35 pack-years) –49% of lung cancer mortality occurred in high- risk patients (with COPD, >35 pack years) HR of dying from lung cancer No COPDCOPD Pack-years

11. MINI02.02: Programmed Cell Death Ligand (PD-L1) Expression in Stage II and III Lung Adenocarcinomas and Nodal Metastases – Uruga H et al Study objective –To compare PD-L1 expression in the main tumour and lymph node metastases of stage II–III ADC and correlate it with survival in patients receiving adjuvant CT Study design –Primary tumour and metastatic lymph node samples from 109 patients with lung ADC were evaluated (PD-L1+, n=53; PD-L−, n=56) Key results –Intratumoural CD8 0/1/2/3: PD-L1+ 7/22/22/2 vs. PD-L1− 28/23/5/0 (p=0.039*) –mRFS: 84 months (PD-L1+) vs. 41 months (PD-L1−); p=0.016 Conclusions –PD-L1 expression was associated with prominent CD8+ TILs –PD-L1 expression in the nodal metastasis follows that in the primary tumour, although no similar –PD-L1 expression in the primary tumour was associated with longer RFS in those who received platinum-based adjuvant therapy Uruga et al. J Thorac Oncol 2015; 10 (suppl 2): MINI02.02 PD-L1 expression in main tumour p-value PositiveNegative PD-L1 expression in N1 lymph nodes Positive304 <0.001 Negative1015 *Multivariate analysis. TILs, tumour infiltrating lymphocytes

12. ORAL13.02: Characterization of PD-L1 Expression Related to Unique Genes in NSCLC Tissue Samples – Garon EB et al Study objective –To assess PD-L1 expression in resected tumour specimens that could potentially guide the design of adjuvant approaches based on immune checkpoint inhibitors Study design –Microarray analyses were performed to assess gene expression for 320 NSCLC and 15 normal lung resection specimens profiled on the Agilent Whole Human Genome 4x44K 2-colour platform –The Rosetta Similarity Tool (ROAST) was used to find genes correlated to PD-L1 expression –Survival analyses based on PD-L1 expression were performed using the Kaplan-Meier method and compared using the log-rank test Key results –PD-L1 expression was higher in NSCLC than breast or endometrial tumours (p<0.01) –Within the 320 NSCLC tissue samples, 174 unique genes are highly correlated with PD-L1 expression (r range= 0.692–0.904) –80 (25%) tissue samples had a PD-L1 log ratio >0, and 63 tissue samples had large sets of highly correlated genes known to be involved in immune and inflammatory response –No significant difference in OS was noted (p=0.661), but increased PD-L1 expression was clearly not associated with better outcomes Conclusion –Within the NSCLC cohort, there is a group of patients with high expression for PD-L1 and related genes; this group does not have a better prognosis vs. those with typical or decreased PD-L1 expression Garon et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL13.02

13. ORAL16.07: Intratumor Heterogeneity of EGFR Activating Mutations Analyzed in Single Cancer Cells in Advanced NSCLC Patients – Guo LH* et al Study objective –To explore the intratumour heterogeneity of EGFR activating mutations in patients with NSCLC Study design –Part 1 investigated the feasibility of single-cell analysis for EGFR exon 21 –Part 2 treated 6 NSCLC patients who had EGFR exon 21 mutation identified by direct sequencing with gefitinib; single-cell analysis of H1975 cells was used to test EGFR exon 21 status and compare the amplification rate of nested PCR and EGFR mutational rate according to PFS >14 months (Group A, n=3) and <6 months (Group B, n=3) Key results –Analysis of 104 single H1975 cells detected EGFR exon mutational status with an amplification rate of 96.2% and an allele drop out rate of 7.0% –135 tumour cells were captured from the samples from the group of 6 patients There was no difference between the groups in amplification rate (84.3% in Group A; 93.8% in Group B; p=0.077) The total mutational rate was higher in Group A than Group B (86.4% vs. 68.9%; p=0.021) Conclusions –It is feasible to perform EGFR mutation detection in single cancer cells and intratumour heterogeneity does exist based on this analysis technique –These data suggest that the abundance of EGFR activating mutation is relevant to the benefit from EGFR-TKI treatment *Presented by Zhang Q Guo et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL16.07

14. ORAL17.03: Biomarkers for Efficacy in JO25567 Study Evaluating Erlotinib plus Bevacizumab versus Erlotinib in Advanced NSCLC with EGFR Mutation – Atagi S et al Study objective –To evaluate exploratory biomarkers of efficacy of bevacizumab + erlotinib in the JO25567 trial Study design –Chemotherapy naïve patients with advanced or recurrent nonsquamous NSCLC, an EGFR mutation and an ECOG PS ≤1 were randomised (1:1) to receive bevacizumab 15 mg/kg q3w + erlotinib 150 mg/day (n=75) or erlotinib 150 mg/day alone (n=77) –Biomarkers for efficacy were analysed: plasma VEFG-A; single nucleotide polymorphisms (SNPs) or variable numbers of tandem repeat (VNTR) Key results –Bevacizumab + erlotinib was associated with significantly higher PFS vs. erlotinib alone in patients with below median VEGF-A (HR 0.23; 95%CI 0.09, 0.60), but not in those with above median VEGF-A (HR 0.56; 95%CI 0.26, 1.25); p=0.033 –No clinically meaningful relationships between any of the SNPs or VNTR were identified –High follistatin levels (p=0.0168) and low leptin levels (p=0.0049) were significantly associated with PFS Conclusions –Low plasma VEGR-A (but not SNPs or VNTR) was associated with better outcomes with bevacizumab + erlotinib –Serum follistatin and leptin were identified as potential biomarkers Atagi et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL17.03

15. ORAL17.07: Mechanisms of Acquired Resistance to AZD9291 in EGFR T790M Positive Lung Cancer – Oxnard GR et al Study objective –To investigate the molecular mechanisms underlying acquired resistance to AZD9291 Study design In patients with T790M-positive lung cancer treated in the AURA trial (phase 1 and 2 components), acquired resistance to AZD9291 was studied using 3 complementary strategies: cell-free DNA (cfDNA) genotyping using droplet digital PCR (ddPCR); next- generation sequencing (NGS) of cfDNA; and molecular analysis of post-AZD9291 disease progression in biopsies Key results –Of 67 patients who met eligibility criteria for resistance, 15 (22%) had detectable C797S on ddPCR, all with detectable T790M –C797S was more common with EFGR exon 19 del (13/43 [30%] vs. those with L858R (2/24 [8%]; p=0.06) –32/67 (48%) had no detectable T790M in plasma despite the presence of the EGFR-TKI- sensitising mutation, suggesting overgrowth of an alternate resistance mechanism Conclusions –At resistance, most patients with resistance to AZD9291 maintain T790M, at times acquiring a new C797S mutation, particularly in those with EGFR exon 19 deletion –At progression, loss of T790M may be mediated by outgrowth of a competing resistance mechanism (e.g. MET or HER2 amplification or BRAF V600E) Oxnard et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL17.07

16. ORAL28.05: Mesothelin and MUC16 (CA125) Are Antigen-Targets for CAR T-Cell Therapy in Primary and Metastatic Lung Adenocarcinoma – Eguchi T et al Study objective –To investigate whether overexpression of mesothelin and/or MUC16 (CA125) affects tumour aggressiveness in patients with stage I lung ADC Study design –Tissue microarrays from tumour and normal lung tissue taken from 912 patients with stage I lung ADC were examined for antigen-expression characteristics and their association with cumulative incidence of recurrence Key results –Univariate analysis found high expression of MUC16 alone, mesothelin alone or both antigens together was associated with significantly increased risk of recurrence than low expression –Multivariate analysis also showed that increased MUC16-mesothelin expression was associated with recurrence (HR 2.57, 95%CI 1.41, 4.68; p=0.002), even after adjustment for known markers of tumour aggression Conclusions –MUC16-mesothelin expression is a marker of tumour aggressiveness in primary lung ADC –These antigens might be candidate targets for CAR T-cell therapy in lung ADC Eguchi et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL28.05

17. PLEN04.05: Multiregion Whole Exome and Transcriptome Sequencing Defines the Genomic Spectrum of EGFR+ NSCLC and Reveals Novel Mechanisms of TKI Resistance – Tan DSW et al Study objective To determine clonal architecture through multi-sector sequencing (Aim 1) and to elucidate mechanisms of EGFR TKI resistance through integrative omics (Aim 2) Study design Aim 1 –Multi-sector sequencing on spatially separated regions from resected EGFR M+ lung adenocarcinoma (9 patients from East Asia, 47 sectors) Aim 2 –30 EGFR M+ TKI resistant samples from 25 patients All samples –Paired tumour-normal exome/transcriptome sequencing and SNP array was performed –Genomic alterations were validated with targeted re-sequencing Tan et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.05

18. PLEN04.05: Multiregion Whole Exome and Transcriptome Sequencing Defines the Genomic Spectrum of EGFR+ NSCLC and Reveals Novel Mechanisms of TKI Resistance – Tan DSW et al Key results –Aim 1 Mutation burden (n=8) (46 sectors) –Per sector: median (range) 48 (9–98) –Per tumour: median (range) 77 (32–146) All EGFR mutations occurred in the trunk T790M was not detected in any sectors with ultra deep sequencing (2000x) Tan et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.05

19. PLEN04.05: Multiregion Whole Exome and Transcriptome Sequencing Defines the Genomic Spectrum of EGFR+ NSCLC and Reveals Novel Mechanisms of TKI Resistance – Tan DSW et al Key results (cont.) –AIM 2 Higher mutation burden in TKI-resistant EGFR M+ NSCLC –TKI naïve vs. resistant (48 vs. 83 median SNVs; p=0.003) Smoking and APOBEC signature were associated with a high mutation burden Recurrent genes of potential significance included MED12 –Modulates EGFR resistance through TGFβR Tan et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.05

20. PLEN04.05: Multiregion Whole Exome and Transcriptome Sequencing Defines the Genomic Spectrum of EGFR+ NSCLC and Reveals Novel Mechanisms of TKI Resistance – Tan DSW et al Conclusions –Genomic architecture of TKI naïve East Asia EGFR M+ NSCLC EGFR mutations are truncal events Low mutation burden Higher clonal diversity (branch/private>trunk) –Mutation burden is relatively higher in TKI-resistant samples Association with smoking and APOBEC signature in a subset of EGFR M+ NSCLC –Multiple potential mechanisms of TKI resistance co-exist For example, MED12 alterations may be subclonal mediators of resistance One patient with co-occurring trunk drivers demonstrated primary TKI resistance Tan et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.05

21. PLEN04.07: Stopping Smoking Reduces Mortality in Low-Dose Computed Tomography (LDCT) Screening Volunteers – Pastorino U et al Study objective To investigate the effect of smoking cessation on the overall mortality of volunteers undergoing low-dose computed tomography (LDCT) screening Study design Follow-up analysis of heavy smokers aged >50 years (n=3,381) who had been enrolled into two LDCT screening programmes between 2000 and 2010 Subjects were divided into three groups: –Current smokers, those who smoked throughout the screening period or stopped <1 year before the end of follow-up or death –Ex-smokers, those who had stopped smoking at the time of accrual / randomisation –Quitters, those who were active smokers at the time of accrual / randomisation but who stopped smoking at least 1 year before the end of follow-up or death The effect of smoking on mortality was adjusted for gender, age, BMI, lung function (FEV 1 %) and pack-years at baseline Pastorino et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.07

22. PLEN04.07: Stopping Smoking Reduces Mortality in Low-Dose Computed Tomography (LDCT) Screening Volunteers – Pastorino U et al Key results –Among 1,801 current smokers, 872 ex-smokers and 708 quitters there were 151, 50 and 59 deaths, respectively –Compared with current smokers, the RR of death of former smokers was 0.74 (95%CI 0.58, 0.95), corresponding to a 26% reduction of total mortality –Excluding 239 subjects who had stopped smoking from <2 years from the end- point of follow-up, RR was 0.61 (95%CI 0.46, 0.80), with a 39% mortality reduction Smoking and mortality Mortality / 100,000 person-years RR, adjusted95%CI Current vs. ex-smoker/quitter846 vs. 7260.740.58, 0.95 Current vs. ex-smoker/quitter >2 years*846 vs. 6130.610.46, 0.80 Current vs. quitter >2 years*846 vs. 5650.570.38, 0.85 Current vs. ex-smoker >2 years*846 vs. 6130.630.46, 0.88 *excluding 239 quitters who stopped smoking <2 years before the end of follow-up or death Pastorino et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.07

23. PLEN04.07: Stopping Smoking Reduces Mortality in Low-Dose Computed Tomography (LDCT) Screening Volunteers – Pastorino U et al Key results (cont.) –Survival curves separated throughout the follow-up period with a p-value of 0.0572 at 9 years Cumulative mortality at 9 years Years 0.12 0.04 0.02 Current Ex-smoker/quitter 9 0.06 0.08 0.10 876543210 Mortality risk p-value log-rank test: 0.0572 0.00 Pastorino et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.07

24. PLEN04.07: Stopping Smoking Reduces Mortality in Low-Dose Computed Tomography (LDCT) Screening Volunteers – Pastorino U et al Conclusions –Stopping smoking is associated with a significant reduction of the overall mortality of heavy smokers enrolled in LDCT screening programs –The benefit of stopping smoking appears to be 3- to 5-fold greater than the one achieved by earlier detection in the NLST trial Pastorino et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.07

25. Early and locally advanced NSCLC Stages I, II and III

26. ORAL04.01: Final Results of Phase III Trial of Adjuvant Chemo-Immunotherapy in Lung Cancer – Kimura H et al Study objective To determine whether the addition of immunotherapy to chemotherapy improves survival Kimura et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL04.01 Primary endpoint OS (5-year rate) Secondary endpoint RFS R PD Key patient inclusion criteria Stage IB–IV NSCLC ECOG PS 0, 1 Age <76 years (n=556) Chemotherapy (n=51) Chemo-immunotherapy* (n=50) *Adoptive transfer of autologous activated killer T cells and dendritic cells (AKT-DC) from the patients’ own regional lymph nodes q8w for 10–14 courses

27. ORAL04.01: Final Results of Phase III Trial of Adjuvant Chemo-Immunotherapy in Lung Cancer – Kimura H et al Key results –Subgroup analysis identified those who were male, had adenocarcinoma, were stage III or had no preoperative chemotherapy to have poorer prognosis with lower HRs –CD8/CD4 ratio was significantly elevated in survivors Conclusions –The use immunotherapy in adjuvant treatment of patients with NSCLC was shown to improve survival –A large-scale multi-institutional trial is required to validate these findings Kimura et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL04.01 Chemo-immunotherapyChemotherapy 2-year OS, %96.064.7 5-year OS, %74.640.9 OS, HR (95%CI); p-value0.321 (1.64, 0.631); p=0.001 2-year RFS, %68.041.2 5-year RFS, %57.229.2 RFS, HR (95%CI); p-value0.435 (0.253, 0.749); p=0.0027

28. ORAL04.03: Preliminary Results of the International Tailored Chemotherapy Adjuvant Trial: The ITACA Trial – Novello S et al Study objective To compare adjuvant pharmacogenomics-driven (personalised) chemotherapy, based on thymidylate synthase (TS) and excision-repair cross-complementing-1 (ERCC1) gene expression versus standard adjuvant chemotherapy Novello et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL04.03 Primary endpoint OS (5-year rate) Secondary endpoints Disease-free interval (DFI), toxicity Stratification Stage II vs. III and smoking status Profile 2: ERCC1 low, TS high Profile 3: ERCC1 high, TS low Profile 1: ERCC1 low, TS low Key patient inclusion criteria Completely resected NSCLC Stage II–IIIA ECOG PS 0–1 (n=761) Profile 4: ERCC1 high, TS, high Cis/pem Control Cis/gem Pemetrexed Taxanes

29. ORAL04.03: Preliminary Results of the International Tailored Chemotherapy Adjuvant Trial: The ITACA Trial – Novello S et al Key results –In total, 386 patients received standard adjuvant therapy and 375 patients received personalised adjuvant therapy –Proportion in each arm: Profile 1, 37.5%; Profile 2, 11.6%; Profile 3, 26.8%; and Profile 4 24.2% –The AEs observed were similar to those observed in other adjuvant trials –For profile 1 (ERCC1 low and TS low), the proportion of discontinuations due to SAEs was significantly higher in the standard vs. personalised adjuvant treatment arms Conclusions –The profile distribution correlated with smoking habit –There was a correlation found between the type of treatment (standard vs. personalised) and toxicity profile –These are interim results, the efficacy data are pending Novello et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL04.03

30. ORAL04.05: Results Ph III Trial Customized Adjuvant CT after Resection of NSCLC with Lymph Node Metastases SCAT: A Spanish Lung Cancer Group Trial – Massuti B et al Study objective –To assess the overall survival in patients treated with BRCA1-based adjuvant chemotherapy after surgical resection of stage II–IIIA NSCLC with lymph node metastases Study design –Patients with resected NSCLC R0, pN1, pN2 (n=591) were randomised (1:3) to control (docetaxel, n=102) and according to BRCA1 levels: T1 (low) received cisplatin/gemcitabine (n=155), T2 (intermediate) received cisplatin/docetaxel (n=99) and T3 (high) received docetaxel (n=100) Key results –In overall population, a trend in OS that favours the experimental has been observed (HR 0.86 [95%CI 0.59, 1.27]) –For low vs. high BRCA1 group HR 0.84 and for intermediate vs. high HR 0.95 –In high BRCA1 group OS HR 1.24 and DFS HR 1.87 and in low BRCA1 group HR 0.50 and 0.64, respectively –In squamous patients for experimental vs. control HR 1.02 (95%CI 0.58, 1.80) and in adenocarcinoma patients HR 0.66 (95%CI 0.39, 1.11) Conclusions –In the overall N+ resected NSCLC population, customising adjuvant chemotherapy according to BRCA1 levels showed a trend towards improved survival –BRCA1 expression levels were associated with histology – higher in those with squamous –In high BRCA1 group, treatment without platinum was inferior to cisplatin/docetaxel –In low BRCA1 group, the non-taxane cisplatin/gemcitabine was superior to cisplatin/docetaxel –In adenocarcinoma patients there was a trend for improved survival in the experimental arms Massuti et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL04.05

31. ORAL04.07: Adjuvant Chemotherapy in Patients with Resected Non-Small-Cell- Lung Cancer Treated with Carboplatin and Oral Vinorelbine - SWITCH I Study – Kolek V et al Study objective –To investigate the efficacy and safety of carboplatin and vinorelbine given intravenously then switched to oral vs. standard adjuvant chemotherapy in radically resected NSCLC Study design –Patients (n=74) aged 18–75 years with complete resection, stage IB (n=19), II (n=30) or IIIA (n=25) NSCLC and ECOG PS 0–1 received carboplatin (D1, AUC5) and vinorelbine 25 mg/m 2 D1 IV switched to 60 mg/m 2 D8 orally for 4 cycles q3w Key results –Mean relative dose intensity was 83.2% for vinorelbine oral, 93.1% for vinorelbine IV and 88.9% for carboplatin –Grade 3–4 AEs included: neutropenia (25.6%), leukopenia (16.2%), alopecia (12.1%), anaemia (8.1%), nausea (4.1%), thrombocytopenia (2.7%), nephrotoxicity (1.4%) and diarrhoea (1.45) –Median OS was 5.90 years (95%CI 3.7, NR) and median disease-specific survival was 7.63 years (95%CI 4.57, NR) –5-year OS was 56.2% and 5-year DSS was 48.4% Conclusion –The use of adjuvant chemotherapy with carboplatin + vinorelbine was tolerable and effective in radically resected NSCLC and comparable to cisplatin-based therapy Kolek et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL04.07

32. ORAL05.02: Quality of Resection in Pathological N2 NSCLC in the Phase 3 Lung Adjuvant Radiotherapy Trial (Lung ART): An Important Factor – Edwards J et al Study objective To explore the impact of post-operative conformal radiotherapy on disease-free survival in patients with completely resected pathologically proven N2 NSCLC with/without induction or adjuvant chemotherapy Edwards et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL05.02 Key patient inclusion criteria Completely resected NSCLC Histologically or cytologically proven N2 nodal involvement No metastasis No previous RT Age >18 years WHO PS ≤1 (n=116) Post-operative conformal RT (54 Gy) PD Primary endpoint DFS Stratification factors Institution, adjuvant chemotherapy, histology, mediastinal lymph node involvement, pretreatment PET-scan R PD Control

33. ORAL05.02: Quality of Resection in Pathological N2 NSCLC in the Phase 3 Lung Adjuvant Radiotherapy Trial (Lung ART): An Important Factor – Edwards J et al Edwards et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL05.02 Key results –Nodal dissection was performed in 71% of the patients as per the recommendations –More than 80% of patients had >2 mediastinal stations explored; station 7 was explored in 106/116 (91%) Conclusion –This analysis suggests that evaluation of the quality of resection in stage IIIA-N2 NSCLC by an external committee is important and that these findings will be useful when interpreting the results of the trial Nodal evaluationn (%) Sampling18 (16) Selective dissection26 (22) Systematic dissection72 (62) Quality of resectionn (%) R050 (43) R uncertain49 (42) R1 because of extra capsular extension16 (14) R2 (this patient should not have been included)1 (1) Reasons for R uncertain (n=49) Incomplete nodal staging9 (18) Involved N2 removed in fragments7 (14) Highest N2 positive30 (61) Incomplete nodal staging + Highest N2 positive3 (6)

34. ORAL05.05: Trimodality Therapy in the Treatment of Stage IIIA Non-Small Cell Lung Cancer (NSCLC): A National Cancer Database Analysis – Behera M et al Study objective To compare the outcomes and predictors associated with trimodality therapy vs. chemoradiotherapy alone in patients with NSCLC from the National Cancer Database Behera et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL05.05 Primary endpoint OS CRT + pneumonectomy CRT alone CRT + lobectomy Key patient inclusion criteria Stage IIIA-N2 (n=29,584) PD

35. ORAL05.05: Trimodality Therapy in the Treatment of Stage IIIA Non-Small Cell Lung Cancer (NSCLC): A National Cancer Database Analysis – Behera M et al Key results –Median OS was 44.5, 25.6 and 15.7 months in CRT + lobectomy, CRT + pneumonectomy and CRT alone (p<0.0001), with 5-year survival rates of 44%, 33% and 14%, respectively –30-day mortality was higher in pneumonectomy vs. lobectomy (7% vs. 2.6%; OR 0.26 [95%CI 0.16, 0.45]); p<0.001) Conclusion –Trimodality therapy demonstrated better outcomes compared with CRT alone in patients with stage IIIA-Ns NSCLC Behera et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL05.05 HR95%CIp-value CRT + lobectomy vs. CRT0.430.38, 0.48<0.001 CRT + pneumonectomy vs. CRT0.570.46, 0.71<0.001 Males vs. females1.191.13, 1.25<0.001 Academic vs. community cancer centres1.141.05, 1.24<0.001 Right vs. left pneumonectomy0.840.55, 1.270.4 CRT + lobectomy vs. CRT with <2 LN0.40.35, 0.46<0.001 CRT + lobectomy vs. CRT with ≥2 LN0.560.46, 0.69<0.001

36. ORAL19.05: Japanese Multicenter Study of Stereotactic Body Radiotherapy for 661 Medically Operable Patients with Stage I Non-Small Cell Lung Cancer – Komiyama T et al Study objective –To investigate the outcome of stereotactic body radiotherapy (SBRT) in medically operable patients with stage I NSCLC Study design –Retrospective analysis of 661 patients from a large, multicentre Japanese database; 486 patients had histologically proven NSCLC –Patients had received a total dose of 32–70 Gy, administered in 4–15 Gy fractions –The median calculated biological effective dose was 107 Gy Key results –Median follow-up for all patients was 35 months –3-year OS and disease-specific survival rates were 79% and 89%, respectively –Multivariate analysis showed only the presence of pulmonary interstitial change was associated with worse survival Komiyama et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL19.05

37. ORAL19.05: Japanese Multicenter Study of Stereotactic Body Radiotherapy for 661 Medically Operable Patients with Stage I Non-Small Cell Lung Cancer – Komiyama T et al Key results –Local progression-free rate at 3 years was better for T1 (89%) than T2 (79%), but there was no difference in OS Conclusion –SBRT may be a promising alternative to surgery for patients with operable stage I NSCLC Komiyama et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL19.05 OS Survival Year 1.0 0.8 0.6 0.4 0.2 0 02468101214 T1 (n=506) T2 (n=155) p=0.55 Local control Survival Year 1.0 0.8 0.6 0.4 0.2 0 024681012 T1 (n=506) T2 (n=155) p=0.004

38. ORAL20.01: A Systematic Review of Carboplatin-Paclitaxel versus Cisplatin- Etoposide Concurrent with Thoracic Radiation for Stage III NSCLC Patients – Steuer C et al Study objective To assess the efficacy and safety of carboplatin-paclitaxel (CP) vs. cisplatin- etoposide (CE) in patients with stage III NSCLC receiving concurrent RT Study design A systematic review was conducted of trials that compared outcomes and toxicities between CP and CE –Trials were excluded if they were phase 1, had fewer than 10 patients or included surgical resection From 2,111 trials identified, 84 trials were included in this analysis: 51 trials evaluating CP (3,789 patients) and 32 trials evaluating CE (2,887 patients) Steuer et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL20.01

39. ORAL20.01: A Systematic Review of Carboplatin-Paclitaxel versus Cisplatin- Etoposide Concurrent with Thoracic Radiation for Stage III NSCLC Patients – Steuer C et al Key results –Anaemia (8% vs. 16%; p=0.06), thrombocytopenia (6% vs. 14%; p=0.001) and neutropenia (23% vs. 54%; p<0.0001) were all lower in the CP vs. CE arm Conclusions –There were no differences in efficacy between the CP and CE arms –Prospective data are required to establish the optimum regimen Steuer et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL20.01 Carboplatin-paclitaxelCisplatin-etoposidep-value ORR, %56580.28 PFS, months9.311.20.15 3-year survival, %25300.5 OS, months18.419.40.35

40. ORAL20.03: Radiation Dose Escalation in Patients with Locally Advanced Non- Small Cell Lung Cancer; 60 Month Follow-Up of a Randomized Phase II Trial – Walraven I* et al Study objective To evaluate the efficacy of dose escalation with hypofractionation in patients with locally advanced NSCLC treated with concurrent cisplatin ± cetuximab *Presented by Belderbos J Walraven et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL20.03 *6 mg/m 2 qd; † 400 mg/m 2 loading dose then 250 mg/m 2 qw Primary endpoint OS R PD Key patient inclusion criteria Inoperable stage II and IIIA/B NSCLC WHO PS 0–1 (n=102) RT (24 x 2.75 Gy) + cisplatin* + cetuximab † (n=51) RT (24 x 2.75 Gy) + cisplatin* (n=51)

41. ORAL20.03: Radiation Dose Escalation in Patients with Locally Advanced Non- Small Cell Lung Cancer; 60 Month Follow-Up of a Randomized Phase II Trial – Walraven I* et al Key results –Median OS was similar in the two groups (33 months in RT + cisplatin group and 30 months in RT + cisplatin + cetuximab; p=0.722) –5-year OS was 36.6% –Squamous histology and comorbidities were associated with worse outcomes and WHO PS was associated with better outcomes Conclusions –OS was exceptionally high with the use of concurrent chemoradiation and hypofractionation (66 Gy /24 fx) although the addition of cetuximab provided no additional benefits –This is a safe and effective treatment and the study is comparable with the RTOG-0167 trial *Presented by Belderbos J Walraven et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL20.03

42. PLEN04.03: Randomized Phase III Trial of Adjuvant Chemotherapy with or without Bevacizumab in Resected Non-Small Cell Lung Cancer (NSCLC): Results of E1505 – Wakelee HA et al Study objective To evaluate the addition of bevacizumab to adjuvant chemotherapy in early stage resected NSCLC Wakelee et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.03 Key patient inclusion criteria Resected Stage IB (≥4 cm)–IIIA 6–12 weeks post-op No prior chemotherapy ECOG PS 0–1 (n=1,501) R 1:1 Arm A: Chemotherapy* x 4 cycles (n=749) Arm B: Chemotherapy* x 4 cycles + bevacizumab 15 mg/kg q3w x 1 yr (n=752) Stratification Cisplatin doublet, stage, histology, gender *Chemotherapy regimens q3w Cisplatin 75 mg/m 2 D1 combined with any of the following: ♦vinorelbine 30 mg/m 2 D1, 8 ♦docetaxel 75 mg/m 2 D1 ♦gemcitabine 1200 mg/m 2 D1, 8 ♦pemetrexed 500 mg/m 2 D1 Primary endpoint: OS Secondary endpoints: DFS, safety

43. PLEN04.03: Randomized Phase III Trial of Adjuvant Chemotherapy with or without Bevacizumab in Resected Non-Small Cell Lung Cancer (NSCLC): Results of E1505 – Wakelee HA et al Key results Wakelee et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.03 Overall survival probability Months from registration 1.0 0.8 0.6 0.4 0.2 0 0 12243648 60 72 84 Chemo (208 events/749 cases) Chemo + bevacizumab (204 events/752 cases) OS HR (B:A) 0.99 95%CI 0.81, 1.21 p=0.93 OS Disease-free survival probability Months from registration 0 12243648 60 72 84 Chemo (338 events/749 cases) Chemo + bevacizumab (334 events/752 cases) DFS HR (B:A) 0.98 95%CI 0.84, 1.14 p=0.75 DFS 1.0 0.8 0.6 0.4 0.2 0

44. PLEN04.03: Randomized Phase III Trial of Adjuvant Chemotherapy with or without Bevacizumab in Resected Non-Small Cell Lung Cancer (NSCLC): Results of E1505 – Wakelee HA et al Key results (cont.) –At 3 months, 61% of patients remained on chemotherapy + bevacizumab –Discontinuation rates at 3 months for chemotherapy were: 17% for AEs, 16% for withdrawal/refusal and 6% for death/progression/other Wakelee et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.03 Reasons off treatment, %Chemotherapy Chemotherapy + bevacizumab Completion of treatment per protocol8237 AEs828 Withdrawal/refusal724 Death on study11 Progression15 Other26

45. PLEN04.03: Randomized Phase III Trial of Adjuvant Chemotherapy with or without Bevacizumab in Resected Non-Small Cell Lung Cancer (NSCLC): Results of E1505 – Wakelee HA et al Key results (cont.) Wakelee et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.03 AEs, % ChemotherapyChemotherapy + bevacizumab G3G4G5G3G4G5 Anaemia87<1 Febrile neutropenia4<151 Myocardial infarction<1 1 Fatigue1014<1 Abdominal pain14 Diarrhoea3<15 Nausea8<110 Vomiting5<17 Lung infection23<1 Wound dehiscence<1 Neutrophil count decreased*16171820 Platelet count decreased2252 Dehydration68<1 Hyponatremia71102 Intracranial haemorrhage<1 Ischaemia cerebrovascular<1- Bronchopleural fistula<1- Bronchopulmonary haemorrhage<1 Hypertension*8281 Peripheral ischaemia<1 Thromboembolic event22<123 Overall worst grade 3–5*4223251303 *Significant difference between treatment groups

46. PLEN04.03: Randomized Phase III Trial of Adjuvant Chemotherapy with or without Bevacizumab in Resected Non-Small Cell Lung Cancer (NSCLC): Results of E1505 – Wakelee HA et al Conclusion –The addition of bevacizumab to adjuvant chemotherapy failed to improve survival for patients with surgically resected early stage NSCLC Wakelee et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.03

47. ORAL35.01: Surgical Approach and Disease Recurrence in NSCLC Patients in the MAGRIT Study – Vallieres E et al Study objective To evaluate surgical approach and recurrence with MAGE-A vs. placebo in patients undergoing R0 resection for NSCLC Vallieres et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL35.01 Descriptive analyses Use of mediastinal lymph node sampling (MLNS) vs. mediastinal lymph node dissection (MLND) as standard of care Patterns of recurrence by type of lymphadenectomy Cox model to assess the prognostic value of lymphadenectomy for DFS and OS R 2:1 PD Stratification Number of chemotherapy cycles; AJCC stage; lymph node sampling; ECOG PS; smoking status Key patient inclusion criteria Histologically-proven, MAGE-A3-positive stage IB–IIIA NSCLC (AJCC 6.0) R0 anatomic resection ECOG PS 0–2 (n=2,272) Placebo (n=757) MAGE-A (n=1,515)

48. ORAL35.01: Surgical Approach and Disease Recurrence in NSCLC Patients in the MAGRIT Study – Vallieres E et al Key results –Lobectomy (including bi- and sleeve-lobectomy) was performed in 85% of patients and 14% required pneumonectomy –MLNS was performed in 53% of patients and MLND in 47% –The proportion of patients who underwent MLNS varied by geographical region: 36% in Europe; 65% in East Asia; 94% in North America; and 59% in other countries –Proportion of patients who experienced recurrence following MLNS and MLND, respectively Any recurrence: 37% and 36% Loco-regional: 40% and 31% Distance: 55% and 64% –There was no prognostic effect of the type of lymphadenectomy on DFS (HR 0.93, 95%CI 0.81, 1.06; p=0.2609) or OS (HR 1.00, 95%CI 0.84, 1.19; p=0.9767) Conclusions –Lobectomy was the most frequently used treatment in the MAGRIT study –Regional differences were observed in treatment used –Although there was some variation in the pattern of recurrence according to the type of lymphadenectomy used this did not impact on prognosis Vallieres et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL35.01

49. ORAL35.02: Wedge Resection vs Segmentectomy for Patients with T1A N0 Non-Small Cell Lung Cancer – Yang CFJ DR et al Study objective To investigate the efficacy and safety of wedge resection vs. segmentectomy in patients with stage T1a N0 NSCLC Patients were identified using the USA National Cancer Data Base After propensity score matching, baseline covariates were balanced between the wedge resection (n=1,231) and segmentectomy (n=1,231) groups Yang et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL35.02 PD Key patient inclusion criteria Stage T1a N0 NSCLC Undergone wedge resection or segmentectomy 2003– 2011 (n=8,785) Segmentectomy (n=1,268) Wedge resection (n=7,517)

50. ORAL35.02: Wedge Resection vs Segmentectomy for Patients with T1A N0 Non-Small Cell Lung Cancer – Yang CFJ DR et al Key results –There were no significant differences between wedge and segmentectomy regarding 30-day mortality (1.6% vs. 1.5%, respectively; p=0.94) –Segmentomy was, however, associated with significantly better long-term survival than wedge resection (median survival of 88.1 months and 5-year survival of 64.9%) –Similar results were found in subgroups of patients with tumours ≤1cm, no comorbidities and pathological T1a pN0 disease Conclusion –Segmentectomy had a similar 30-day mortality as wedge resection but improved long-term survival in all patient groups studied Yang et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL35.02 Time (months) 0.50 0.25 Wedge resection Segmentectomy 60 0.75 1.00 483624120 Overall survival (probability) 75.4 88.1 58.6 64.9 Median survival (months) 5-year survival (%) Log-rank p-value <0.01 0.00

51. Advanced NSCLC Not radically treatable stage III and stage IV 1 st line

52. ORAL03.05: Clinical Outcomes with Pemetrexed-Based Systemic Therapy in RET-Rearranged Lung Cancers – Drilon A et al Study objective –To explore the benefits of pemetrexed-based treatment in RET-rearranged lung cancers relative to other genomic subsets Study design –Data for 104 patients with advanced stage IIIB–IV NSCLC were retrospectively reviewed to compare PFS, ORR (RECIST v1.1), TTP and OS between RET-rearranged lung cancers (n=18) and control (ROS1-rearranged [n=10], ALK-rearranged [n=36] and KRAS-mutant lung cancers [n=41]) groups Key results –Median pack-year cigarette smoking history significantly differed between groups (p<0.001): RET 0 (0–48 range), ROS1 0 (0–48), ALK 0 (0–74) and KRAS 38 (0–93) –The line of pemetrexed therapy (first vs. other, p=0.119), type of therapy (platinum combination, non-platinum combination vs. single-agent, p=0.144) and need for dose reduction (p=0.977) did not differ between groups Conclusion –RET-rearranged lung cancers are sensitive to pemetrexed-based therapy with a durable clinical benefit observed that is comparable to ALK- and ROS1-rearranged lung cancers and improved compared with KRAS-mutant lung cancers Drilon et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL03.05 ORR, %DCR, %mPFS, monthsmOS, monthsmTTP, months RET-rearranged459120NR ROS1-rearranged789023NR32 ALK-rearranged50932437NR KRAS-mutant26836a6a 16 b 7a7a a KRAS significantly different to ALK, ROS1 and RET; b KRAS significantly different to ALK and RET

53. Advanced NSCLC Not radically treatable stage III and stage IV Later lines

54. ORAL01.02: Therapy of Advanced Metastatic Lung Cancers with an Anti-Trop-2- SN-38 Antibody-Drug Conjugate, IMMU-132: Interim Phase II Clinical Results – Camidge DR et al Study objective To investigate the safety and efficacy of sacituzumab govitecan (IMMU-132), a new antibody drug conjugate (ADC), in advanced metastatic lung cancers Camidge et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL01.02 R PD Key patient inclusion criteria Patients with NSCLC or SCLC Previously treated (n=54) IMMU-132 10 mg/kg D1, D8 q3w (n=31) IMMU-132 8 mg/kg D1, D8 q3w (n=23) Primary endpoint ORR per RECIST v1.1, safety Secondary endpoints PFS

55. ORAL01.02: Therapy of Advanced Metastatic Lung Cancers with an Anti-Trop-2- SN-38 Antibody-Drug Conjugate, IMMU-132: Interim Phase II Clinical Results – Camidge DR et al Camidge et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL01.02 Key results Conclusion –IMMU-132 monotherapy is well tolerated in heavily pretreated NSCLC and SCLC patients Tumour type Prior lines of therapy: median (range)ORR, %DCR, % Median PFS, months (maturity, %) 8 mg/kg10 mg/kg NSCLC (n=19)3 (1–8)32743.4 (62)5.4 (56) SCLC (n=20)2.5 (1–7)30552.0 (87)4.6 (83) Grade 3–4 AEs occurring >2% of patients, % 8 mg/kg (n=23) 10 mg/kg (n=31) 8 & 10 mg/kg (n=54) Neutropenia221015 Diarrhoea904 Leukopenia466 Anaemia936 Atrial fibrillation904 Hyperglycaemia434 Hyponatremia904 Lymphopenia434 Febrile neutropenia032

56. ORAL02.01: Phase 3, Randomized Trial (CheckMate 017) of Nivolumab (NIVO) vs Docetaxel in Advanced Squamous (SQ) Cell Non-Small Cell Lung Cancer (NSCLC) – Reckamp K et al Study objective –To evaluate updated efficacy and safety results comparing nivolumab vs. docetaxel in advanced squamous cell NSCLC Study design –Patients who had received 1 prior platinum-based chemotherapy regimen with ECOG PS 0–1 and pretreatment tumour samples for PD-L1 analysis were randomised to nivolumab 3 mg/kg q2w (n=135) or docetaxel 75 mg/m 2 q3w (n=137) until disease progression or toxicity Key results Reckamp et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL02.01 OutcomeNivolumabDocetaxelHR (95%CI); p-value OS, months9.26.00.62 (0.48, 0.81); p=0.0004 12-mo OS, %4224 18-mo OS, %2813 PFS, months3.52.80.63 (0.48, 0.83); p=0.0008 ORR, %209p=0.0083 Grade 3–5 treatment-related AE, %858

57. ORAL02.01: Phase 3, Randomized Trial (CheckMate 017) of Nivolumab (NIVO) vs Docetaxel in Advanced Squamous (SQ) Cell Non-Small Cell Lung Cancer (NSCLC) – Reckamp K et al Key results (cont.) –Most treatment-related AEs were experienced in the first 3 months of treatment: Conclusions –With longer follow-up, nivolumab continued to demonstrate survival benefit vs. docetaxel in previously- treated patients with advanced squamous NSCLC –Nivolumab benefit was independent of PD-L1 expression and seen across all clinical subgroups –The safety profile of nivolumab continues to be favourable vs. docetaxel and consistent with prior studies Reckamp et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL02.01

58. ORAL02.03: Longer-Term Follow-Up of a Phase 2 Study (CheckMate 063) of Nivolumab in Patients with Advanced, Refractory Squamous Non-Small Cell Lung Cancer – Horn L et al Study objective –To assess updated safety and survival of nivolumab in patients with squamous NSCLC who progressed during or after prior platinum-doublet chemotherapy and ≥1 additional systemic regimens Study design –Patients with stage IIIB/IV squamous NSCLC and ECOG PS 0–1 received nivolumab 3 mg/kg q2w until PD or toxicity Key results –Any grade TEAEs occurring in ≥10% of patients included: fatigue, decreased appetite, nausea, asthenia, rash and diarrhoea Conclusion –Nivolumab continues to provide clinically meaningful efficacy with no new safety concerns in patients with advanced squamous NSCLC Horn et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL02.03 Nivolumab 3 mg/kg Median OS, months (95%CI)8.1 (6.1, 10.9) PD-L1 <1%8.3 (5.6, 15.6) PD-L1 ≥1%10.1 (5.5, 16.8) 1-year OS rate, % (95%CI)39 (30, 48) 18-month OS rate, % (95%CI)27 (19, 35)

59. ORAL02.05: Safety and Efficacy of First-Line Nivolumab (NIVO; Anti- Programmed Death-1 [PD-1]) and Ipilimumab in Non-Small Cell Lung Cancer (NSCLC) – Rizvi NA et al Study objective –To evaluate the safety and efficacy of first-line therapy with nivolumab plus ipilimumab in chemotherapy-naïve patients with advanced NSCLC Study design –Patients with stage IIIB/IV NSCLC (any histology), who had received no prior chemotherapy for advanced disease and ECOG PS 0 or 1 were randomised to nivolumab 1 mg/kg + ipilimumab 1 mg/kg both q3w, nivolumab 1 mg/kg q2w + ipilimumab 1 mg/kg q6w, nivolumab 3 mg/kg q2w + ipilimumab 1 mg/kg q12w or nivolumab 3 mg/kg q2w + ipilimumab 1 mg/kg q6w Key results Conclusions –First-line therapy with nivolumab plus ipilimumab demonstrated high level of clinical activity with durable responses –Nivolumab plus ipilimumab is associated with a manageable safety profile Rizvi et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL02.05 Outcome NIVO 1 + IPI 1 q3w NIVO 1 q2w + IPI 1 q6w NIVO 3 q2w + IPI 1 q12w NIVO 3 q2w + IPI 1 q6w Treatment-related AEs leading to discontinuation, any grade, %138510 Treatment-related AEs leading to discontinuation, grade 3–4, %1083 Confirmed overall response, %13253931 Median PFS, months10.64.98.08.3 24-week PFS, %55NC63NC

60. ORAL03.01: Anlotinib as 3rd-Line Treatment for Refractory Advanced NSCLC: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial – Han B et al Study objective –To investigate the efficacy and safety of anlotinib in patients with refractory NSCLC Study design –Patients ≥18 years with metastatic or recurrent advanced NSCLC and ECOG PS 0–1 were randomised (1:1) to receive anlotinib 12 mg/day orally D1–14 q3w (n=60) or placebo (n=57) until progression, unacceptable toxicity, withdrawal or death –RECIST (version 1.1) criteria were used to assess response and progression –Primary endpoint: PFS; secondary endpoints: ORR, OS, biomarkers and safety Key results –PFS was prolonged with anlotinib vs. placebo (4.83 vs. 1.23 months, HR 0.32 [95%CI 0.20, 0.51]; p<0.0001) –ORR was improved with the addition of anlotinib vs. placebo (10% vs. 0%; p=0.03) –DCR was 83.33% with anlotinib vs. 31.58% with placebo (p<0.0001) –Subgroup analyses of data stratified by age, gender, smoking, metastases number and EGFR status showed PFS benefit for anlotinib vs. placebo group –mOS was prolonged with anlotinib vs. placebo (10.33 vs. 6.3 months, HR 0.656; Log-rank p=0.0752) –The most common grade 3 AEs were hypertension, hand-foot skin reaction and increased triglycerides Conclusion –Anlotinib as a third-line treatment appears to provide significant PFS benefits in patients with refractory advanced NSCLC with no serious safety concerns Han et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL03.01

61. ORAL03.06: Activity of Crizotinib in MET Amplified NSCLC: Preliminary Results of the AcSé Trial – Moro-Sibilot D et al Study objective –To identify subsets of patients who may benefit from crizotinib 250 mg bid treatment who have MET amplified (+) tumours explored as part of the French National Cancer Institute AcSe program Study design –170 participating centres across France; target testing through the 28 French NCI (INCa) labelled molecular genetic centres –MET+ was explored by FISH in tumour samples showing an IHC score of 2+ or 3+ –Patients with ECOG 0–2 and a tumour showing >6 MET copies were eligible, providing they were not eligible for any another trial evaluating a MET inhibitor –ORR and DCR were assessed q8w, using RECIST v1.1 Key results –Median age of patients (n=25) was 59 years (range 30–92) and median treatment duration was 2.8 months (range 12 days–14 months); 84% had adenocarcinoma and 100% had metastatic disease at study entry –At best response, ORR was 32% [8/25] (95%CI 9, 45) and DCR was 60% [15/25] (95%CI 41, 79) –No correlation was observed between the number of MET copies and response at 2 cycles (p=0.19) or at best response (p=0.10) –Crizotinib was well tolerated; most common AEs, mainly grade 1 or 2, were: visual disorders, nausea, anaemia, vomiting, fatigue and elevated transaminases Conclusions –Nationwide biomarker-driven access to crizotinib for patients with MET+ malignancy is feasible –Crizotinib was well tolerated and showed responses in pretreated MET+ lung cancers Moro-Sibilot et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL03.06

62. ORAL03.07: Response to crizotinib and cabozantinib in Stage IV Lung NSCLC Patients with Mutations That Cause MET Exon 14 Skipping – Paik P et al Study objective –To investigate responses to crizotinib and cabozantinib in patients with stage IV lung adenocarcinomas harbouring mutations leading to MET exon 14 skipping and report the clinical characteristics associated with this genotype Study design –Patients with stage IV NSCLC harbouring MET exon 14 splice site mutations (n=26) or a mutation deleting Y1003 in exon 14 (n=1) were identified through a clinical assay based on hybrid capture/next- generation sequencing of 341 oncogenes and tumour suppressors (MSK-IMPACT) –Radiographic response to MET inhibition was assessed using RECIST 1.1 and PERCIST criteria Key results –Overall, 56% patients had smoking history and 70% had adenocarcinoma –Patients were treated with off-label crizotinib (n=7), crizotinib on a clinical trial (n=8; NCT00585195) or cabozantinib (n=1; NCT01639508) –To date, 5 patients have been treated with off-label crizotinib and 1 with cabozantinib and crizotinib Four of six patients (66.7%) developed a PR to crizotinib treatment, including one patient who had previously received cabozantinib and had shown SD by RECIST and PET imaging demonstrating a complete PERCIST response to treatment initially The remaining 2 patients on off-label crizotinib have their first scan pending Conclusions –MET exon 14 skipping is a novel oncogenic target that can predict response to MET inhibitors –Patients with these splice site mutations should be treated on a clinical trial of a MET inhibitor Paik et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL03.07

63. MINI03.01: Prior TKI Therapy in NSCLC EGFR Mutant Patients Associates with Lack of Response to Anti-PD-1 Treatment – Garon EB et al Study objective To determine the relationship between prior TKI therapy and response to anti-PD-1 therapy in patients with NSCLC EGFR mutations (EGFRm) Study design In vitro –Western blot analysis of PD-L1 expression in NSCLC cell lines in response to erlotinib and afatinib Clinical –Retrospective analysis of patients from KEYNOTE-001clinical trial in which patients received pembrolizumab 2 mg/kg q3w or 10 mg/kg q2–3w –Patients Early in the trial, patients with EGFRm were excluded; a subsequent amendment required patients to have a known EGFR status Those with EGFR sensitising mutations must have had documented disease progression on erlotinib, gefitinib or afatinib and documented disease progression on subsequent platinum-double chemotherapy Garon et al. J Thorac Oncol 2015; 10 (suppl 2): MINI03.01

64. MINI03.01: Prior TKI Therapy in NSCLC EGFR Mutant Patients Associates with Lack of Response to Anti-PD-1 Treatment – Garon EB et al Key results –In vitro PD-L1 levels decrease in response to EGFR TKI in cell lines sensitive to TKI –Clinical Among 29 EGFRm patients in KEYNOTE-001, 2 of 3 EGFR-naïve patients achieved a PR vs. 1 of 26 with a history of prior EGFR TKI (p<0.001) 18 of these patients had a 9-week follow-up scan –Both of the EGFR TKI-naïve patients achieved a PR compared with only 1 of 16 with a history of prior EGFR TKI (p<0.001) The 1 patient with a history of prior EGFR TKI therapy who achieved a PR harboured an exon 20 insertion In EGFR wild-type patients, prior TKI did not affect RR (p<0.601) A lower proportion of EGFRm patients continued on trial to the 9-week scan (62% [18/29]), compared with EGFR wild-type patients (87% [60/69]) Conclusions –There was a strong correlation between response and lack of prior EGFR TKI treatment, especially in those with a sensitising mutation –PD-L1 levels decreased in response to an EGFR in cell lines sensitive to TKI –PD-1/PD-L1 inhibition prior to an EGFR TKI may be more efficacious than a strategy in which the PD-1/PD-L1 inhibition follows, or is given concurrently with an EGFR TKI Garon et al. J Thorac Oncol 2015; 10 (suppl 2): MINI03.01

65. MINI03.05: Efficacy of Pembrolizumab in Key Subgroups of Patients with Advanced NSCLC – Hellmann MD et al Study objective –To assess the relationship between anti-tumour activity and the level of PD-L1 expression in key patient subgroups Study design (KEYNOTE-001) –Treatment: pembrolizumab 2 mg/kg q3w, 10 mg/kg q3w or 10 mg/kg q2w until confirmed progression, intolerable toxicity or investigator decision –PD-L1 expression: Assessed by IHC using a clinical assay and 22C3 antibody –Patients (n=550) Evaluable patients for PD-L1 had slides prepared within 6 months and for which a total proportion score (TPS) could be assigned Key subgroups analysed: –Histology, smoking status, mutational status Hellmann et al. J Thorac Oncol 2015; 10 (suppl 2): MINI03.05

66. MINI03.05: Efficacy of Pembrolizumab in Key Subgroups of Patients with Advanced NSCLC – Hellmann MD et al Key results –Within all subgroups, higher TPS (≥50% vs. 1–49% and <1%) was associated with improved outcome (i.e., ORR, PFS and OS) –EGFR wild-type was associated with higher ORR vs. EGFR mutant for TPS ≥50% (39.8% vs. 20.0%), TPS 1–49% (12.2% vs. 8.7%) and TPS <1% (12.7% vs. 0%) –KRAS mutation had no significant effect on ORR Conclusions –In all subgroups examined, improved response was observed in patients with PD-L1 TPS ≥50% vs. those with less PD-L1 expression –The interdependency between PD-L1 status, mutational status and smoking history will be further explored in ongoing randomised trials, including KEYNOTE-010 Hellmann et al. J Thorac Oncol 2015; 10 (suppl 2): MINI03.05 Odds Ratio (95%CI)p-valueInteraction p-value HistologySquamous— 0.630.81 Nonsquamous1.16 (0.62, 2.08) Smoking historyNever— 0.0090.27 Current or former2.50 (1.27, 4.89) PD-L1 TPS<50%— <0.0001— ≥50%4.45 (2.27, 7.13)

67. ORAL31.02: Pembrolizumab for NSCLC: Immune-Mediated Adverse Events and Corticosteroid Use – Leighl N et al Study objective –To examine the incidence of immune-mediated AEs and use of corticosteroids in the management of patients with NSCLC (n=550) in the KEYNOTE-001 trial Study design –Patients received pembrolizumab at 2 mg/kg q3w (n=61), 10 mg/kg q3w (n=287) or 10 mg/kg q2w (n=202) Key results –The most common immune-mediated AEs were: hypothyroidism (7.6%), pneumonitis (3.8%) and infusion reactions (3.5%) and mainly occurred with the first 2–4 months Conclusions –Management using pembrolizumab interruption and steroid use for the most severe events was successful –This limited data suggests that there is no clear relationship between continued pembrolizumab efficacy and steroid use Leighl et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL31.02 Steroid useNo steroid use ORR, % (95%CI)32.1 (15.9, 52.4)19.5 (16.2, 23.2) DCR, % (95%CI) 64.3 (44.1, 81.4)49.6 (45.2, 54.0) PFS, months (95%CI)4.6 (2.1, 6.2)3.4 (2.6, 4.1) OS, months (95%CI)11.4 (5.0, NR)13.5 (10.6, 15.5)

68. MINI03.09: Role of T790M Mutation in EGFR-TKI Rechallenge for Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer – Zhang Q-Y et al Study objective To retrospectively evaluate the role of T790M mutation in EGFR-TKI rechallenge after failure of initial EGFR-TKIs in EGFR-mutant advanced NSCLC Study design Data were analysed retrospectively from 515 patients with stage IIIB/IV EGFR- mutant NSCLC who had previously received gefitinib or erlotinib –Of these, 51 patients had EGFR exon 19 or 21 L858R mutations and underwent rebiopsy after failure (at resistance) of initial EGFR-TKIs followed by EGFR-TKI rechallenge EGFR detection was performed by Sanger sequencing or Amplification Refractory Mutation System methods PFS and OS data were analysed using the Kaplan-Meier method and log-rank test EGFR activating mutations still existed in all the 51 patients who received rebiopsy: –18 patients had T790M mutations and 33 patients were without T790M mutations Zhang et al. J Thorac Oncol 2015; 10 (suppl 2): MINI03.09

69. MINI03.09: Role of T790M Mutation in EGFR-TKI Rechallenge for Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer – Zhang Q-Y et al Zhang et al. J Thorac Oncol 2015; 10 (suppl 2): MINI03.09 Key results Conclusions –EGFR T790M mutation is not related to clinical outcomes in EGFR-TKI rechallenge in patients with advanced NSCLC and EGFR mutation –A larger prospective study based on biomarkers is warranted in the future GroupNMedian in months 95% confidence interval T790M−332.01.1, 2.9 T790M+181.81.2, 2.4 PFS (%) Time (Months) 1.0 0.8 0.6 0.4 0.2 0246812 p=0.261 PFS 10 GroupNMedian in months 95% confidence interval T790M−336.83.3, 10.3 T790M+187.74.9, 10.5 OS (%) Time (Months) 1.0 0.8 0.6 0.4 0.2 01020304060 p=0.754 OS 50 0.0 + +

70. MINI05.08: Comparison of the Efficacy of Dacomitinib v Erlotinib for NSCLC Pts with Del 19/L858R – Ramalingam SS et al Study objective –To compare the clinical activity of dacomitinib vs. erlotinib in advanced NSCLC in patients with EGFR mutations, including common activating mutations (CAMs) Study design –EGFR mutation status was determined using a pooled database of two RCTs* (dacomitinib 45 mg/day, n=119; erlotinib 150 mg/day, n=103) Key results Conclusion –This subgroup analysis suggests a favourable efficacy profile for dacomitinib vs. erlotinib in NSCLC in patients with common activating EGFR mutations, but this requires further prospective validation Ramalingam et al. J Thorac Oncol 2015; 10 (suppl 2): MINI05.08*ARCHER 1009 and A7471028; † unstratified mPFS, monthsDacomitinibErlotinibHR † (95%CI)p-value EGFR mutations (n=121)10.99.60.815 (0.542, 1.224)0.160 EGFR CAMs in exon 19 or 21 (n=101)14.69.60.717 (0.458, 1.124)0.073 EGFR CAMs in exon 19 (n=78)14.610.00.585 (0.335, 1.024)0.029 EGFR CAMs in exon 21 (n=33)10.09.00.955 (0.421, 2.168)0.458

71. ORAL18.02: MUC1-Targeted Dendritic Cell-Based Vaccine Immunotherapy in Patients with Standard Treatments-Refractory Non-Small-Cell Lung Cancer – Teramoto K et al Study objective –To evaluate the efficacy of MUC1-targeted dendritic cell-based vaccine immunotherapy in patients with advanced NSCLC who are refractory to standard treatments Study design –Patients (n=41) with histologically- or cytologically-confirmed NSCLC, ECOG PS 0–2 were administered subcutaneous MUC1-targeted dendritic cell-based vaccine immunotherapy q2w –Tumour responses were assessed in 29 patients Key results –Median number of vaccinations was 6 (range 1–42) –Across all patients the median OS from first vaccination was 7.4 months (95%CI 4.5, 10.3); 1-year survival rate was 29.3% (95%CI 15.3, 41.2) –In patients who received >6 vaccinations (n=29), median OS was 10.1 months (95%CI 8.3, 11.9) from the first vaccination and 1-year survival rate was 41.4% (95%CI 23.5, 59.3) –Patients with immune-related AEs or peripheral white blood cells >20% had the best prognosis Conclusion –MUC1-targeted dendritic cell-based vaccine immunotherapy demonstrated interesting early activity in patients with NSCLC refractory to standard treatments Teramoto et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL18.02

72. PLEN04.01: A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without Concurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): SWOG S081 – Herbst R et al Study objective To evaluate the effect of adding cetuximab to carboplatin/paclitaxel or carboplatin/paclitaxel/bevacizumab in patients with advanced NSCLC Herbst et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.01 Key patient inclusion criteria Newly diagnosed or recurrent stage IV NSCLC (n=1,333) R 1:1 Paclitaxel + carboplatin + bevacizumab* (n=657) Paclitaxel + carboplatin + bevacizumab* + cetuximab (n=656) Bevacizumab* + cetuximab Stratification Appropriate use of bevacizumab, smoking status, stage M1a vs. M1b Secondary endpoints ♦OS and PFS by bevacizumab appropriate, safety Primary endpoint ♦OS (entire study), PFS (EGFR FISH) *In appropriate patients

73. PLEN04.01: A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without Concurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): SWOG S081 – Herbst R et al Key results Herbst et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.01 PFS NEvents Median, months95%CI 65653610.99.6, 12.0 6575589.48.7, 10.3 Survival probability (%) Months after registration 100 80 60 40 20 0 0 122436 4860 HR 0.94 95%CI 0.84, 1.06 p=0.34 OS 656 657 287 246 76 94 28 36 5656 1111 446 448 153 141 48 50 11 13 2222 Cetuximab Control Patients at risk: Months after registration 0 12 60 HR 0.98 95%CI 0.87, 1.09 p=0.68 656 657 66 56 11 19 4848 1111 0000 217 215 29 30 5 11 2424 0101 Cetuximab Control NEvents Median, months95%CI 6566294.64.2, 5.2 6576324.54.2, 4.9 Patients at risk: 0 2436 48 100 80 60 40 20

74. PLEN04.01: A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without Concurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): SWOG S081 – Herbst R et al Key results (cont.) –Grade 3–4 AEs occurring in >10% in any group included: blood/bone marrow, metabolic/laboratory, gastrointestinal, infection and dermatology/skin –Grade 5 AE included gastrointestinal, infection and pulmonary/upper respiratory Herbst et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.01 Analysis group PFS, HR (95%CI)OS, HR (95%CI); p-value All patientsFISH+All patientsFISH+ All patients (n=1,313)0.98 (0.87, 1.09) p=0.68 0.91 (0.74, 1.12) p=0.37 0.94 (0.84, 1.06) p=0.34 0.83 (0.67, 1.04) p=0.10 Bevacizumab appropriate (n=554) 1.05 (0.88, 1.25) p=0.57 1.07 (0.77, 1.47) p=0.70 1.04 (0.86, 1.25) p=0.70 0.97 (0.69, 1.38) p=0.88 Bevacizumab inappropriate (n=759) 0.93 (0.80, 1.07) p=0.31 0.82 (0.63, 1.07) p=0.14 0.88 (0.76, 1.03) p=0.12 0.75 (0.57, 1.00) p=0.048 Squamous cell carcinoma (n=321) 0.88 (0.70, 1.11) p=0.29 0.68 (0.46, 1.01) p=0.06 0.85 (0.67, 1.08) p=0.18 0.56 (0.37, 0.84) p=0.006

75. PLEN04.01: A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without Concurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): SWOG S081 – Herbst R et al Conclusions –In the overall study population there was no benefit in OS for adding cetuximab –In EGFR+ population, there was no benefit in PFS when adding cetuximab –There was an indication of benefit for OS in the EGFR FISH+ population, but this was not statistically significant –There was an indication of benefit on OS among bevacizumab-inappropriate EGFR FISH+ patients –In squamous cell FISH+ patients a significant improvement in OS was observed although this is an exploratory objective Herbst et al. J Thorac Oncol 2015; 10 (suppl 2): PLEN04.01

76. ORAL31.06: An Exploratory Responder Analysis of Best RECIST Response and Survival in Patients with Metastatic Squamous NSCLC Treated with Nivolumab – Kazandjian D et al Study objective –To investigate the association between response and OS in patients with metastatic squamous NSCLC receiving anti-PD1 therapy with nivolumab Study design –Patients with metastatic squamous NSCLC (n=117) received nivolumab 3 mg/kg IV q2w until PD or toxicity –Patients were grouped according to RECIST response into responders and non- responders Key results Conclusions –There is a correlation between response and survival, but the results should be interpreted with caution owing to the exploratory retrospective nature of this analysis Kazandjian et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL31.06 ResponseMedian OS, months (95%CI) SD12.7 (8.0, 15.7) PD with treatment beyond PD10.9 (6.6, NR) PD with treatment discontinuation4.6 (3.5, 6.5) Response at month 3.5Median months from month 3.5 (95%CI) ResponderNR Non-responder7.4 (4.5, 10.1)

77. Other malignancies SCLC and mesothelioma

78. ORAL10.01: A DLL3-Targeted ADC, Rovalpituzumab Tesirine, Demonstrates Substantial Activity in a Phase I Study in Relapsed and Refractory SCLC – Rudin CM et al Rudin et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL10.01 Study objective To report preliminary results of a first in-human phase 1 trial in patients with recurrent SCLC treated with rovalpituzumab tesirine (a DLL3-targeted antibody-drug conjugate) monotherapy R 2:1 PD Key patient inclusion criteria SCLC with PD after 1–2 previous lines of therapy DLL3+ positive (n=52) Rovalpituzumab tesirine* q6w (n=18) Rovalpituzumab tesirine* q3w (n=34) *Escalated dosing schedule: 0.05, 0.1, 0.2, 0.4 and 0.8 mg/kg

79. ORAL10.01: A DLL3-Targeted ADC, Rovalpituzumab Tesirine, Demonstrates Substantial Activity in a Phase I Study in Relapsed and Refractory SCLC – Rudin CM et al Rudin et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL10.01 Key results –Maximum tolerated doses: 0.2 mg/kg q3w x3 cycles; 0.3 mg/kg q6w x2 cycles –Among the 16 confirmed DLL3+ patients, 7 (44%) patients had PR and 8 (50%) patients had SD for a combined clinical benefit rate of 94% –In all evaluable patients (n=32), the ORR was 22% (n=7 PR) and SD 53% (n=17), for a combined clinical benefit rate of 75% –Similar response rates were observed among patients sensitive and refractory to first-line therapy and in the third-line setting –The most common TEAEs were: fatigue (40%), rash (39%), nausea (29%), dyspnoea (23%), decreased appetite (21%) and vomiting (21%) Conclusions –Rovalpituzumab tesirine monotherapy had significant anti-tumour activity and a manageable toxicity in patients with recurrent DLL3+ SCLC –A pivotal study is being planned

80. ORAL10.04: Pembrolizumab for ED SCLC: Efficacy and Relationship with PD-L1 Expression – Ott PA et al Study objective To assess the safety and efficacy of pembrolizumab in patients with PD-L1-positive SCLC in the on-going multi-cohort phase 1b KEYNOTE-028 study Ott et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL10.04 Primary endpoint(s) ORR per RECIST v1.1 and safety Secondary endpoints PFS, OS, duration of response Pembrolizumab 10 mg/kg IV q2w Key patient inclusion criteria SCLC Failure or inability to receive standard therapy ≥1 measurable lesion PD-L1 positivity ECOG PS 0–1 (n=24) CR, PR, SD Confirmed PD a /toxicity Discontinue treatment Treat for 24 months / until progression a / intolerable toxicity Response assessment q8w for 1 st 6 months; q12w thereafter a If clinically stable patient to stay on treatment until progression confirmed on 2 nd scan ≥4 weeks later

81. ORAL10.04: Pembrolizumab for ED SCLC: Efficacy and Relationship with PD-L1 Expression – Ott PA et al Ott et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL10.04 Key results –mDOR: 29.1 weeks (0.1, 29.1) –PFS: 1.8 months (95%CI 1.6, 8.5); 6-month PFS: 32.5% –There was no relationship between higher PD-L1 expression on tumour and inflammatory cells and frequency of response (p=0.235) Conclusions –Pembrolizumab showed promising anti-tumour activity in patients with pretreated, PD-L1- positive SCLC –The safety profile was consistent with previous trials in other tumour types –Higher PD-L1 expression did not correlate with frequency of response Grade 3–5 AEs occurring in ≥1 patient, n (%)n=24 Any2 (8.3) Asthenia1 (4.2) Blood bilirubin increased1 (4.2) Colitis1 (4.2) Intestinal ischaemia1 (4.2) Best overall responsen (%)95%CI CR00.0, 14.2 PR7 (29.2)12.6, 51.1 SD1 (4.2)0.1, 21.1 PD10 (41.7)22.1, 63.4

82. ORAL10.06: Long-Term Survival after Surgery for Pathologic N1 and N2 Small Cell Lung Cancer: A Comparison with Nonoperative Management – Yang C-F et al Study objective To test whether or not surgery, in the setting of modern adjuvant therapies, offers a survival advantage among patients with node-positive SCLC compared with non- operative management Study design Patients were identified between 2003 and 2011 from the National Cancer Data Base: –Patients had to have pT1–2 N1–2 M0 SCLC –All patients underwent non-operative management (CT ± RT ≥45 Gy) or surgery (with adjuvant CT ± RT ≥45 Gy) –Patients with a history of unrelated malignancy and palliative-intent treatment were excluded Data were assessed using Kaplan-Meier analyses and propensity score matching Yang et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL10.06

83. ORAL10.06: Long-Term Survival after Surgery for Pathologic N1 and N2 Small Cell Lung Cancer: A Comparison with Nonoperative Management – Yang C-F et al Key results Conclusions –Surgery + adjuvant CT ± RT was associated with better survival vs. non- operative management in patients with node-positive SCLC –Results support the re-evaluation of the role of surgery for selected patients Yang et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL10.06 mOS, monthsSurgeryNo surgeryp-value pN136.217.1<0.01 pN222.613.3<0.01 OS OS (probability) 1.00 0.75 0.50 0.25 0.00 Time (months) 01224364860 Log-rank p-value <0.01 Median survival5-year survival Surgery26.3 months28.5% No surgery17.1 months16.7%

84. ORAL11.02: Phase I Study of Anti-Mesothelin Antibody Drug Conjugate Anetumab Ravtansine – Hassan R et al Study objective To evaluate the safety, pharmacokinetics and tumour response in patients with advanced solid tumours treated with anetumab, with a particular focus on patients with mesothelioma Hassan et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL11.02 Key patient inclusion criteria Histologically or cytologically confirmed solid tumours Tumour types with known high expression of mesothelin (n=77) Primary endpoints Safety, tolerability, PK and MTD Secondary endpoints Tumour response Anetumab ravtansine IV q3w Dose-escalation cohort a (n=45) MTD expansion cohort (n=32) 38 patients received anetumab ravtansine at the MTD (6.5 mg/kg q3w): 16 mesothelioma, 21 ovarian cancer, 1 breast cancer a Includes 6 patients treated at the MTD (6.5 mg/kg q3w) PD

85. ORAL11.02: Phase I Study of Anti-Mesothelin Antibody Drug Conjugate Anetumab Ravtansine – Hassan R et al Hassan et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL11.02 Key results Conclusion –Anetumab ravtansine at the MTD (6.5 mg/kg q3w) showed encouraging efficacy with durable partial response in patients with advanced mesothelioma Drug-related AEs in ≥10% of patients, n (%) 0.15–4.5 mg/kg a q3w (n=26) 5.5 mg/kg q3w (n=9) 6.5 mg/kg q3w (n=6) 7.5 mg/kg q3w (n=4) MTD expansion 6.5 mg/kg q3w (n=32) GradeAny3 or 4Any3 or 4Any3 or 4Any3 or 4Any3 or 4 Nausea6 (23.1)02 (22.2)03 (50.0)02 (50.0)019 (59.4)2 (6.3) Fatigue6 (23.1)04 (44.4)02 (33.3)01 (25.0)016 (50.0)4 (12.5) Blurred vision/keratitis0000004 (100)1 (25.0)17 (53.1)2 (6.3) Diarrhoea001 (11.1)03 (50.0)00010 (31.3)1 (3.1) Neuropathy1 (3.8)02 (22.2)0001 (25.0)011 (34.4)1 (3.1) Vomiting3 (11.5)0003 (50.0)01 (25.0)09 (28.1)1 (3.1) Anorexia4 (15.4)0002 (33.3)00010 (31.3)0 Increased AST00001 (16.7) 2 (50.0)07 (21.9)0 Increased ALT1 (3.8)0001 (16.7)01 (25.0)05 (15.6)0 a Combined data from cohorts 1 (0.15 mg/kg q3w) to 7 (4.5 mg/kg q3w) n (%) All patients treated at MTD (n=38) Mesothelioma patients treated at MTD All patients (n=16)1 prior line of systemic cytotoxic treatment n=10) CR PR SD PD 0 7 (18.4) 18 (47.4) 10 (26.3) 0 5 (31.3) 7 (43.8) 4 (25.0) 0 5 (50.0) 4 (40.0) 1 (10.0) ORR (CR or PR) DCR (CR, PR, or SD) 7 (18.4) 25 (65.8) 5 (31.3) 12 (75.0) 5 (50.0) 9 (90.0)

86. ORAL11.03: Single-Agent Pembrolizumab for Patients with Malignant Pleural Mesothelioma (MPM) – Alley EW et al Study objective To report updated safety, efficacy and survival data in patients with malignant pleural mesothelioma (MPM) treated with pembrolizumab in the KEYNOTE-028 study Alley et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL11.03 Key patient inclusion criteria Locally advanced or metastatic MPM Failure of / inability to receive standard therapy ECOG PS 0 or 1 ≥1 measurable lesion PD-L1 positivity No autoimmune or ILD (n=25) Primary endpoints ORR per RECIST v1.1, safety Secondary endpoints PFS, OS, DOR Pembrolizumab 10mg/kg IV q2w CR, PR, SD Confirmed progressive disease a / unacceptable toxicity Discontinue treatment Treat for 24 months / until progression a / intolerable toxicity Response assessment q8w for 1 st 6 months; q12w thereafter a If clinically stable patient to stay on treatment until progression confirmed on 2 nd scan ≥4 weeks later

87. ORAL11.03: Single-Agent Pembrolizumab for Patients with Malignant Pleural Mesothelioma (MPM) – Alley EW et al Alley et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL11.03 Key results –Median PFS was 5.8 months (95%CI 3.4, 8.2) and 6-month PFS rate was 50.0% –There was no relationship between higher PD-L1 expression on tumour and inflammatory cells and frequency of response Conclusion –Single-agent pembrolizumab showed significant clinical activity in patients with PD-L1– positive MPM but further evaluation is required Best overall responsen%95%CI Complete response a 000.0, 13.7 Partial response a 728.012.1, 49.4 Stable disease1248.027.8, 68.7 Progressive disease416.04.5, 36.1 No assessment b 28.01.0, 26.0 Objective response rate a : 28.0% (95%CI 12.1, 49.4) Disease control rate a : 76.0% (95%CI 54.9, 90.6) a Both confirmed and unconfirmed responses are included b Includes patients who discontinued therapy before the first post-treatment scan due to progressive disease

88. ORAL26.01: Initial Analyses of the IASLC Malignant Pleural Mesothelioma (MPM) Database: Implications for the 8th Edition AJCC and UICC Staging Manuals – Rusch V et al Study objective To determine whether outcomes from the MPM database analysis warrant revisions to the upcoming 8 th edition of the AJCC/UICC staging manuals Study design Electronic data capture to a new data dictionary used for case submissions Minimum case submission requirements: complete clinical and/or post-surgical TNM stage with anatomical descriptors to support stage designation; accurate survival information; no conflict between descriptors and reported stage; and node positivity recorded by individual station OS was analysed by Kaplan-Meier Significance of individual T, N and M descriptors was evaluated by log-rank and Cox regression Rusch et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL26.01 AJCC, American Joint Committee on Cancer; UICC, Union for International Cancer Control

89. ORAL26.01: Initial Analyses of the IASLC Malignant Pleural Mesothelioma (MPM) Database: Implications for the 8th Edition AJCC and UICC Staging Manuals – Rusch V et al Key results –3,519 cases were submitted; 2,450 were included –Stage available: clinical only 34%; post-surgical only 33%; both 34% –A total of 1,982 (81%) cases underwent surgery –5-year OS for any N, MO showed no difference for T1a vs. T1b or for post- surgical T2 vs. T3 –5-year OS for any T, MO showed no difference for N1 vs. N2 Conclusion –These initial results suggest some changes in the current MPM staging system are warranted, especially regarding T categories, although additional analyses are ongoing Rusch et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL26.01

90. ORAL26.02: What Are the Risks and Benefits of Extended Pleurectomy Decortication for Mesothelioma? A Review of the Largest Institutional Series in the UK – Sharkey AJ et al Study objective To assess the efficacy and safety of extended pleurectomy decortication (EPD) in patients with mesothelioma Study design Retrospective analysis of case notes and pathological reports of 266 patients who underwent EPD within the previous 15 years Duration of hospital stay, complication rates and survival were investigated Key results Across all patients studied the median OS was 12.2 months Epithelioid pNO disease was the most favourable subgroup with longer survival rate at 1, 3 and 5 years and longer overall median duration of survival Sharkey et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL26.02 OS rate (%) Median OS (months) 1 year3 years5 years All patients48.010.32.712.2 Epithelioid pNO64.917.55.223.1

91. ORAL26.02: What Are the Risks and Benefits of Extended Pleurectomy Decortication for Mesothelioma? A Review of the Largest Institutional Series in the UK – Sharkey AJ et al Key results –The most common post-operative complication was persistent air leak and occurred in 31.0% of patients, followed by atrial fibrillation in 16.7% –Duration of intercostal drainage was significantly associated with the development of empyema (p<0.001) and dehiscence of the neodiaphragm (p=0.042) –Re-operation was required in 30 (11.3%) patients –Post-operative complications significantly lengthened the median hospital stay by 26 days with empyema (p<0.001), 7 days with removal of prosthetic patch (p=0.003) and 6 days each with persistent air leak (p<0.001) and atrial fibrillation (p=0.037) –90-day mortality was significantly higher in patients who developed pleural empyema (71.4% vs. 8.6%, p=0.001) –Complications prevented chemotherapy use in 28% of patients with empyema and 22.7% of those with neodiaphragm dehiscence Conclusions –In all but a selected subgroup of patients, EPD remains a palliative procedure –Reducing postoperative air leak, which increases pleural sepsis and perioperative risk and decreases adjuvant chemotherapy, is paramount Sharkey et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL26.02

92. Other malignancies Rare tumours

93. ORAL06.01: Genomic Characterization of Large-Cell Neuroendocrine Lung Tumors – Fernandez-Cuesta L et al Study objective –To perform genomic analyses of large-cell neuroendocrine carcinoma (LCNEC) using in house developed and published pipelines Study design –6.0 SNP array analyses of 60 LCNECs, exome sequencing of 55 tumour-normal pairs, genome sequencing of 11 tumour-normal pairs, transcriptome sequencing of 69 tumours and expression arrays on 60 tumours were performed Key results –Integrative analyses of copy number, mutations and expression patterns defined 2 major groups of LCNEC SCLC-like group – with MYCL1 and IRS2 amplifications, concomitant mutations in RB1 (27%) and TP53 (75%) genes and inactivation of both TP53 and RB1, which is the hallmark of SCLC, in 20% of the cases AD/SQ-like group – harbouring mutations in KEAP1 (22%) and STK11 (23%) Conclusions –Although these results suggest that LCNEC might be a mix of different lung cancer subtypes, mutation clonality and expression analyses show that they are likely to be a separate entity, sharing molecular characteristics with the other lung cancer subtypes –The heterogeneity of the two groups suggests that LCNEC might represent an evolutionary trunk that can branch to SCLC or AD/SQ Fernandez-Cuesta et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL06.01

94. ORAL11.05: Phase II Trial of Single Agent Amrubicin in Patients with Previously Treated Advanced Thymic Malignancies – Wakelee HA et al Study objective To investigate the safety and efficacy of amrubicin, a third-generation anthracycline and topoisomerase II inhibitor, in patients with previously treated advanced thymic malignancies Wakelee et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL11.05 Primary endpoint ORR Secondary endpoints PFS, DCR, toxicity Amrubicin* 40 mg/m 2 IV D1, 2, 3 per 21d cycle PD Key patient inclusion criteria Inoperable invasive thymoma or thymic carcinoma Adequate bone marrow, hepatic, renal + cardiac function (n=33) *Modified to 35 mg/m 2 due to high febrile neutropenia

95. ORAL11.05: Phase II Trial of Single Agent Amrubicin in Patients with Previously Treated Advanced Thymic Malignancies – Wakelee HA et al Key results –mPFS: 8.5 months (95%CI 6.7, inf.); OS: 30.1 months (95%CI 21.6, inf.) Conclusions –Amrubicin monotherapy shows promise in previously treated patients with thymic malignancies –Toxicity was as expected with a high frequency of febrile neutropenia Wakelee et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL11.05 n (%)All (n=33)Thymoma (n=14)Thymic carcinoma (n=19) PR6 (18)4 (29)2 (11) SD23 (70)10 (71)13 (68) PD4 (12)0 (0)4 (21) DCR29 (88)14 (100)15 (79) Grade 3– 4 AEs occurring in ≥10% of patients, n (%)All (n=33) Fatigue7 (21) Febrile neutropenia7 (21) Anaemia4 (12)

96. ORAL11.06: A Prospective Phase II Study of Cisplatin and Cremophor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors: Can 18F-FDG PET/CT play a role? – Kim HS et al Study objective To investigate the efficacy and safety of cisplatin plus cremophor EL-free paclitaxel (Genexol- PM) in patients with unresectable thymic epithelial tumours (TETs) Kim et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL11.06 Cisplatin 70 mg/m 2 + Genexol-PM 230 mg/m 2 q3w Treat until maximum 6 cycles PD intolerance Key patient inclusion criteria Unresectable TETs (thymoma / thymic carcinoma) No prior palliative chemotherapy Measurable disease (RECIST 1.1) Age ≥18 years ECOG PS 0–1 (n=42) Primary endpoint ORR Secondary endpoints PFS, toxicity, predictive value of the early response using PET-CT

97. ORAL11.06: A Prospective Phase II Study of Cisplatin and Cremorphor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors: Can 18F-FDG PET/CT play a role? – Kim HS et al Key results –There were no treatment-related deaths; the most common grade 3/4 treatment-related AE was neutropenia in 11 (26%) patients –Early metabolic response assessed by PET CT was not correlated to PFS in responders vs. non- responders (9.2 vs. 12.7 months; p=0.232) Conclusion –The combination of cisplatin and Genexol-PM is highly effective and tolerable for the treatment of unresectable TETs, especially in patients with thymic carcinoma Kim et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL11.06 Patients, n (%); 95%CIAll (n=40)Thymoma (n=13)Thymic carcinoma (n=27) OR*25 (62.5); 47.6, 77.46 (46); 23.3, 76.919 (70); 52.0, 82.1 SD13 (32.5); 17.6, 52.37 (54); 23.1, 76.76 (22); 3.8, 40.6 PD2 (5.0); 0, 12.40 (0)2 (8); 0, 14.8 *OR includes only PR; there was no CR Progression-free survival Time (months) 1.0 0.8 0.2 030 PFS 6121824 + + + + + + + + + + + + 0.6 0.4 mPFS: 9.8 months 0.0 Median follow-up: 15.7 months Overall survival Time (months) 1.0 0.8 0.2 036 OS 6121830 0.6 0.4 mOS: not reached 2-year OS: 71% 24 ++++++++ +++ +++ + +++++++++ + +++ 0.0

98. Other malignancies Brain metastases

99. ORAL16.01: Tyrosine Kinase Inhibitors (TKIs) for the Treatment of Brain Metastases (BMs) from Advanced Lung Cancer: A Large Retrospective Cohort – Bennati C et al Study objective –To evaluate the efficacy of TKIs in treating brain metastases in patients with advanced NSCLC Study design –Retrospective analysis of 89 patients with NSCLC and brain metastases and known mutation status: ALK+, 33 (37.1%); EGFR+, 38 (42.7%); ALK/EGFR- controls, 18 (20.2%) –Standard radiotherapy (WBRT or radiosurgery) was used prior to TKIs in 40/71 (56.3%) patients, while the remainder received a TKI upfront: EGFR inhibitor (gefitinib/erlotinib/afatinib) in 13/38 (34.2%); ALK TKI (crizotinib/ceritinib/alectinib) in 18/33 (54.5%) Key results –OIRR was achieved in 81.5% of the EGFR+ cohort and 84.8% of the ALK+ subset with TKI given either before or after radiotherapy –Among those who were treated with TKIs upfront the OIRR was 100%, including complete response in 4/18 (22.2%) of patients with ALK+ Conclusions –TKIs are strongly active in patients with brain metastases from NSCLC which harbour an EGFR or ALK driver alteration –First-line use of TKIs may be reasonable in asymptomatic patients with long survival expectation, for whom WBRT may be postponed until a later disease stage Bennati et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL16.01OIRR, overall intracranial response rate

100. ORAL31.07: A Phase II Trial of Pembrolizumab for Untreated Brain Metastases from Non-Small Cell Lung Cancer – Goldberg SB et al Study objective –To determine the safety and efficacy of pembrolizumab in patients with advanced NSCLC and untreated or progressive brain metastases Study design –Patients with advanced NSCLC and at least 1 untreated or progressive brain metastases (5–20 mm), ECOG PS 0–1 received pembrolizumab 10 mg/kg q2w Key results –At interim analysis, the brain metastases response (CR + PR) rate was 33% –Of 6 patients with systemic response, 5 had response in CNS –Duration of brain metastases response was ~6 months –4 of 5 confirmed responses are still ongoing –Median OS 7.7 months (95%CI 3.5, NR) –There were 4 treatment-related grade ≥3 AE: fatigue, diarrhoea, pneumonitis and hypokalaemia Conclusions –Pembrolizumab appears to have activity in CNS in patients with NSCLC and untreated brain metastases –Systemic immunotherapy for select patients with small, asymptomatic brain metastases may be an alternative to radiation warranting further study Goldberg et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL31.07