1. Tanguy Seiwert, MD Assistant Professor, Department of Medicine Associate Director, Head and Neck Cancer Program Section of Hematology/Oncology Fellow, Institute for Genomics and Systems Biology University of Chicago Chicago, Illinois Current and Future Directions for the Treatment of Metastatic Head and Neck Squamous Cell Carcinoma This program is supported by an educational grant from

2. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Faculty Tanguy Seiwert, MD Assistant Professor, Department of Medicine Associate Director, Head and Neck Cancer Program Section of Hematology/Oncology Fellow, Institute for Genomics and Systems Biology University of Chicago Chicago, Illinois Tanguy Seiwert, MD, has served as a consultant for Bayer, Boehringer-Ingelheim, Novartis, and Onyx and has received research support from Genentech/Roche.

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4. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Overview  HNSCC background  Systemic treatment options for HNSCC –Cytotoxic chemotherapy for HNSCC –Current EGFR therapies –Emerging EGFR therapies  Other emerging targets for HNSCC

5. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Anatomic Sites of Head and Neck Cancer  Heterogeneous group of cancers; varying primary sites  Squamous histology in 95% of cases  Anatomic sites –Oral cavity –Nasopharynx/oropharynx/hypopharynx –Larynx  Other anatomic sites –Paranasal sinuses –Lip –Salivary glands 1. Adapted from: SEER training modules, head & neck cancer. National Institutes of Health, National Cancer Institute. Oral Cavity Lip Buccal mucosa Alveolar ridge Retromolar trigone Floor of mouth Hard palate Oral tongue (anterior two thirds) Larynx Supraglottis Glottis Subglottis Nasal Cavity Tongue Esophagus Jaw Nasopharynx Oropharynx Base of tongue Soft palate Tonsillar pillar and fossa Hypopharynx Pharynx

6. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma HNSCC: Overview  6th most common cancer worldwide [2] –650,000 cases and 200,000 deaths/yr worldwide [2] –~ 54,000 new cases/year in the US [3] ; most common cancer in central Asia  2 different etiologies and corresponding tumor types –Tobacco smoking and alcohol consumption (HPV-) –Infection with high-risk HPV (HPV+); largely limited to oropharyngeal cancers  HPV+ tumors are distinct entity with better prognosis and may require differential treatments  Given recent genomic studies, etiology of differential biology of HPV+ and HPV- is now increasingly evident [4,5] 2. Globocan Project. Geneva: World Health Organization; 2010. 3. Siegel R, et al. CA Cancer J Clin. 2013;63:11-30. 4. Wilting SM, et al. BMC Med Genomics. 2009;2:32. 5. Hayes DN, et al. ASCO 2013 Clinical Science Symposium. Abstract 6009.

7. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma HNSCC: Survival Rates by Stage of Disease  High cures rates are achieved for localized and loco-regional disease using: –Surgery –Radiation –Chemoradiation –± Induction chemotherapy  Survival rates for recurrent/ metastatic disease remain very poor  Better treatment options are necessary 6. SEER. Stat fact sheets: oral cavity and pharynx cancer. 2003-2009. 5-Yr Relative Survival Rate by Stage at Diagnosis [6] Survival (%) LocalizedDistant 83% 59% Regional 36% 0 20 40 60 80 100

8. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma HNSCC: Etiology  In Western countries, there has been major change in the etiology of HNSCC with the rapid rise of HPV-related oropharyngeal cancers HPV-Positive HNSCCHPV-Negative HNSCC Anatomic site [7-9] Oropharynx (tonsil/base of tongue, soft palate)All sites/upper aerodigestive tract Histology [10] BasaloidKeratinized Age [9,11] Younger; healthierOlder; higher rate of comorbidities Sex [12] 3:1 men (unclear why)3:1 men (due to tobacco use) Socioeconomic statusTends to be highTends to be low Risk factors [9,11,13] Sexual behaviorTobacco Cofactors [14,17,19] Marijuana/immune suppression (eg, HIV)Tobacco/alcohol Incidence [11,12] Rising rapidlyDeclining Survival [9,13] ImprovedWorse 2nd cancers [11] UncommonCommon (including lung cancer) 7. Smith EM, et al. J Natl Cancer Inst. 2004;96:449-455. 8. Herrero R. J Natl Cancer Inst Monogr. 2003;31:47-51. 9. Fakhry C, et al. J Clin Oncol. 2006;24:2606-2611. 10. Poetsch M, et al. Head Neck. 2003;25:904-910.11. Chaturvedi AK, et al. J Clin Oncol. 2008;26:612-619. 12. Cole L, et al. PLoS One. 2012;7:e32657. 13. Ritchie JM, et al. Int J Cancer. 2003;104:336-344. 14. Gillison ML, et al. J Natl Cancer Inst. 2008;100:407-420. 17. D’Souza G, et al. J Acquir Immune Defic Syndr. 2013. [ePub ahead of print] 19. D’Souza G, et al. N Engl J Med. 2007;356:1944-1956.

9. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma 21. Chaturvedi AK, et al. J Clin Oncol. 2011;29:4294-4301. The HPV “Epidemic” in the United States 10 1 0.1 100 10 1 0.1 20,000 15,000 10,000 5000 0 1988-1990 1991-19921995-19961999-2000 2003-2004 1980 199520102025 2010 2020 2030 Oropharynx (overall) HPV+ oropharynx HPV- oropharynx Rates per 100,000 Annual Number of Cases Cervix Oropharynx (overall) Oropharynx (men) Oropharynx (women) Cervix Oropharynx (overall) Oropharynx (men) Oropharynx (women) 2010

10. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma HNSCC: HPV Survival Advantage  OS by HPV status in TAX 324 [22]  Risk classification according to most influential prognostic factors to predict OS [23] –43% low risk: HPV+ with ≤ 10 pk- yrs or > 10 pk-yrs and N0-N2a cancer –30% intermediate risk: HPV+ with > 10 pk-yrs or HPV ‒ with ≤ 10 pk- yrs and T2-T3 cancer –27% high risk: HPV ‒ with ≤ 10 pk- yrs and T4 cancer or > 10 pk-yrs –3-year OS: 93.0% low-risk group, 70.8% intermediate-risk group, and 46.2% high-risk group 22. Posner MR, et al. Ann Oncol. 2011;22:1071-1077. 23. Ang KK, et al. N Engl J Med. 2010;363:24-35. HPV+ HPV- 1.00 0.80 0.60 0.40 0.20 0 0 12 24 36 48 60 72 84 96 108 120 Survival Time, months HPV+ HPV- Pts at Risk, n HPV+ HPV- 56 53 51 49 42 40 35 20 13 3 55 58 27 23 22 20 10 6 3 2 P = 6.63e-8 Survival Distribution Function

11. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Relationship Between HPV and EGFR Expression in HNSCC  High EGFR gene copy number and protein expression associated with poor clinical outcome in advanced HNSCC [24-26]  Significant proportion of HNSCC, particularly oropharyngeal cancers, caused by HPV infection [27] –High-risk HPV subtype 16 accounts for 85% of all HPV+ tumors in HNSCC [28] –p16 used as surrogate marker of HPV infection in HNSCC but is only useful in the oropharynx –More accurate HPV testing is available and based on E6/E7 detection [29]  HPV+ tumors show significantly lower EGFR expression levels than HPV- HNSCC; EGFR amplification only occurs in HPV- HNSCC [30,31] 24. Chung CH, et al. J Clin Oncol. 2006;24:4170-4176. 25. Kumar B, et al. J Clin Oncol. 2008;26:3128-3137. 26. Chung CH, et al. Int J Radiat Oncol Biol Phys. 2011;81:331-338. 27. Chung CH, et al. Clin Cancer Res. 2009;15:6758- 6762. 28. Dayyani F, et al. Head Neck Oncol. 2010;2:15. 29. Liang C, et al. Cancer Res. 2012;72:5004-5013. 30. Young RJ, et al. Cancer Epidemiol Biomarkers Prev. 2011;20:1230-1237. 31. Hayes DN, et al. TCGA ASCO 2013. Abstract 6009.

12. Treatment Options for Recurrent/Metastatic HNSCC

13. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Recurrent/Metastatic HNSCC: Cytotoxic Agents  Active cytotoxic agents –Cisplatin, carboplatin, 5-FU, taxanes, methotrexate, ifosfamide, gemcitabine (for NPC), bleomycin, others –Methotrexate is FDA approved for use with HNSCC but no longer commonly used in the US  First-line therapy –For patients with good PS: historically platinum-based doublet (eg, cisplatin/5-FU or carboplatin/paclitaxel) –ORR: 30% to 40%; median OS: 6-9 mos regardless of specific drugs –Cetuximab commonly added to current treatment regimens –For patients with poor PS: use single agent or cetuximab  Second-line therapy: taxanes, methotrexate, cetuximab 32. NCCN. Clinical practice guidelines in oncology: head and neck cancers. v.2.2013.

14. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Anti-EGFR Therapy: Cetuximab  Cetuximab is a chimeric IgG1 anti-EGFR antibody –May also stimulate immune system via ADCC  Approved for HNSCC as a single agent, [33] with chemotherapy (EXTREME study), [34] with radiation (Bonner study) [35]  Efficacy data –Despite high EGFR expression levels in HNSCC, single- agent response rate is “only” 13% with SD rate of 33% [33] –There is currently NO predictive biomarker available 33. Vermorken JB, et al. J Clin Oncol. 2007;25:2171-2177. 34. Vermorken JB, et al. N Engl J Med. 2008;359:1116-1127. 35. Bonner JA, et al. N Engl J Med. 2006;354:567-578.

15. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma EXTREME: Platinum/5-FU With or Without Cetuximab in Recurrent/Metastatic HNSCC  Randomized phase III trial  Primary endpoint: OS  Secondary endpoints: PFS, ORR, DCR, TTF, DoR, QoL, safety Cetuximab maintenance 36. Vermorken JB, et al. N Engl J Med. 2008;350:1116-1127. Recurrent/metastatic HNSCC; no previous chemotherapy except for locally advanced disease > 6 mos prior to study entry; no nasopharyngeal carcinoma (N = 442) No maintenance PD or toxicity PD or toxicity Up to 6 cycles: cetuximab 400 mg/m 2, then 250 mg/m 2 /wk until PD or unacceptable toxicity; carboplatin AUC 5 or cisplatin 100 mg/m 2 on Day 1; 5-FU 1000 mg/m 2 on Days 1-4 every 3 wks. Cetuximab + Carboplatin or Cisplatin + 5-FU (n = 222) Carboplatin or Cisplatin + 5-FU (n = 220)

16. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma 127 153 83 118 65 82 47 57 19 30 173 184 220 222 8 15 1313 HR : 0.80 (95% CI: 0.64-0.99; P =.04) Chemotherapy only (n = 220)20 Chemo + cetuximab (n = 222)36 Survival Probability 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 03691215182124 10.1 mos 7.4 mos Pts at Risk, n CTX only CET + CTX Survival Time (Mos) Cetuximab ± First-line Platinum in Recurrent or Metastatic HNSCC: OS ORR, % 37. Vermorken JB, et al. N Engl J Med. 2008;350:1116-1127.

17. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Cetuximab ± First-line Platinum in Recurrent or Metastatic HNSCC: Safety 38. Vermorken JB, et al. N Engl J Med. 2008;350:1116-1127. Grade 3/4 AEs in ≥ 5% of Pts, n (%) Cetuximab + Chemotherapy (n = 219) Chemotherapy Alone (n = 215)P Value* Grade 3/4Grade 4Grade 3/4Grade 4 Any event179 (82)67 (31)164 (76)66 (31).19 Neutropenia49 (22)9 (4)50 (23)18 (8).91 Anemia29 (13)2 (1)41 (19)2 (1).12 Thrombocytopenia24 (11)0 3 (1)1.00 Leukopenia19 (9)4 (2)19 (9)5 (2)1.00 Skin reactions20 (9)01 (< 1)0<.001 Hypokalemia16 (7)2 (1)10 (5)1 (< 1).31 Cardiac events16 (7)11 (5)9 (4)7 (3).22 Vomiting12 (5)06 (3)0.23 Asthenia11 (5)1 (< 1)12 (6)1 (< 1).83 Anorexia11 (5)2 (1)3 (1)1 (< 1).05 Hypomagnesemia11 (5)8 (4)3 (1)1 (< 1).05 Febrile neutropenia10 (5)2 (1)10 (5)4 (2)1.00 *Comparing Grade 3 and 4 combined.

18. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma 39. Vermorken JB, et al. Lancet Oncol. 2013;14:697-710. SPECTRUM: Cisplatin + 5-FU ± Panitumumab in Recurrent/Met HNSCC  Open-label, randomized phase III trial  Primary endpoint: OS  Secondary endpoints: PFS, ORR, DOR, TTR, safety Patients with distant metastatic and/or locally recurrent HNSCC, ECOG PS ≤ 1 (N = 657) Stratified by previous treatment, primary tumor site, ECOG PS Optional panitumumab maintenance q3w Panitumumab 9 mg/kg Day 1 Cisplatin 100 mg/m 2 Day 1 5-FU 1000 mg/m 2 Days 1-4 (n = 327) Cisplatin 100 mg/m 2 Day 1 5-FU 1000 mg/m 2 Days 1-4 (n = 330) Max six 3-wk cycles

19. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Cisplatin + 5-FU ± Panitumumab in Recurrent/Met HNSCC: OS  Subgroup analysis in p16-negative patients significant: 11.7 vs 8.6 mos (P =.01) –Despite questions about p16 IHC cutoff values, hypothesized that EGFR inhibitors may be ineffective in HPV+ tumors –Supported by lack of EGFR overexpression/amplification in HPV+ tumors HR: 0.87 (95% CI 0.73–1.05) P =.14 40. Vermorken JB, et al. Lancet Oncol. 2013;14:697-710. 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 Mos 100 80 60 40 20 0 Overall Survival (%) Panitumumab 11.1 (9.8-12.2) Control 9.0 (8.1-11.2) Median OS, months (95% CI)

20. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Cisplatin + 5-FU ± Panitumumab: Safety AEs of Interest in ≥ 5% of Pts From Any Arm, % Panitumumab Group (n = 325) Control Group (n = 325) Grade 3/4Grade 4Grade 3/4Grade 4 Patients with any event67306625  Skin or eyes, or both19220  Hypomagnesaemia12541  Hypokalaemia10373  Stomatitis or oral mucositis9191  Cardiac arrhythmias6122  Dehydration5120  Diarrhea5< 11 Hematologic toxicity43204517  Neutropenia32133312  Anemia122142  Thrombocytopenia6382  Febrile neutropenia6452 41. Vermorken JB, et al. Lancet Oncol. 2013;14:697-710.

21. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Additional Anti-EGFR TKIs in HNSCC  Previously small molecule anti-EGFR TKI have been less effective for HNSCC  Afatinib: an irreversible EGFR/erbB2/erbB4 blocker (pan-HER blockade) –Evaluated for HNSCC vs cetuximab Cohen 2003 [42] Cohen 2005 [43] Kirby 2006 [44] Soulieres 2004 [45] Agent Gefitinib 500 mg Gefitinib 250 mg Gefitinib 500 mg Erlotinib 150 mg Median PFS or TTP, mos3.41.82.62.2 Median OS, mos8.15.54.36.0 1-yr OS, %29.219020 ORR, %10.61.484.3 42. Cohen EE, et al. J Clin Oncol. 2003;21:1980-1987. 43. Cohen EE, et al. Clin Cancer Res. 2005;11:8418-8424. 44. Kirby AM, et al. Br J Cancer. 2006;94:631-636. 45. Soulieres D, et al. J Clin Oncol. 2004;22:77-85.

22. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Phase II Study: Afatinib vs Cetuximab in Recurrent/Metastatic HNSCC Stage 1Stage 2 Continue until PD or undue AEs CT/MRI every 8 wks Afatinib 50 mg/day PO Cetuximab Cetuximab 400/250 mg/m 2 /wk IV Stratum: number of previous chemotherapies for R/M disease (0 or 1) Continue until PD or undue AEs 48. Seiwert T, et al. Multidisciplinary Head and Neck Cancer Symposium 2012. Abstract LBPV10. Primary endpoint: tumor shrinkage of target lesions in S1 Metastatic/recurrent HNSCC after failure of platinum-based regimen (N = 124; 62 per arm) Afatinib

23. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Maximum Tumour Shrinkage in Target Lesions 23 ≥ 20%n = 8 ≥ 0% - < 20% n = 16 > -30% - < 0%n = 10 ≤ -30%n = 16 Afatinib (n = 50) Maximum Decrease From Baseline (%) Patient Index Sorted by Maximum % Decrease ≥ 20%n = 12 ≥ 0% - < 20% n = 17 > -30% - < 0%n = 19 ≤ -30%n = 7 Cetuximab (n = 55) Maximum Decrease From Baseline (%) Patient Index Sorted by Maximum % Decrease 49. Seiwert T, et al. Multidisciplinary Head and Neck Cancer Symposium 2012. Abstract LBPV10. Investigator ReviewIndependent Central Review AfatinibCetuximabAfatinibCetuximab Total randomized, n62 ORR (CR, PR), n (%) 95% CI 10 (16.1) 8.0-27.7 4 (6.5) 1.8-15.7 5 (8.1) 2.7-17.8 6 (9.7) 3.6-19.9 P value.09-- 50010203040 130 110 90 70 50 30 10 -10 -30 -50 -70 -90 -110 -130 130 110 90 70 50 30 10 -10 -30 -50 -70 -90 -110 -130 6001020304050

24. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Afatinib vs Cetuximab: Treatment Duration  Data suggest that afatinib may overcome cetuximab resistance in a fraction of patients; potential lack of cross-resistance 0100200300400500600700 0 10 20 30 40 50 60 Afatinib Cetuximab Treatment Exposure, days Patients Index, n Cetuximab Afatinib Afatinib DC Cetuximab DC 0100200300400500600700 0 10 20 30 40 50 60 Treatment Exposure, days Patient Index, n 50. Seiwert T, et al. ASCO 2013. Abstract 6001. Afatinib DC Cetuximab DC

25. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma 51. ClinicalTrials.gov. NCT01345682. 52. ClinicalTrials.gov. NCT01345669. LUX - Head & Neck 1 [51] LUX - Head & Neck 2 [52] Afatinib: Ongoing Phase III Studies N = 474 Afatinib 40 mg once daily MTX 40 mg/m 2 IV weekly Randomized 2:1 Continuous treatment until PD (or AEs requiring withdrawal) Randomized, open-label phase III trial; second- line treatment: patients have progressed on previous platinum-based chemotherapy for recurrent/metastatic HNSCC Primary endpoint: PFS N = 669 Afatinib 40 mg once daily Placebo 40 mg once daily Randomized post-CRT 2:1 Treatment for 18 mos (or until recurrence or unacceptable AEs) Randomized, double-blind, placebo-controlled phase III trial; primary unresected, stage III-IVB HNSCC; disease free (with or without neck dissection) after completed previous CRT Primary endpoint: DFS

26. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Other EGFR-Targeted Agents in Development  Dacomitinib: EGFR/erbB2/erB4 irreversible TKI –Activity in HNSCC in single phase II trial [53]  MEHD7945A: EGFR/HER3 antibody –Currently in phase II testing for HNSCC vs cetuximab [54] –Phase I data: MEHD7945A may overcome cetuximab resistance; heregulin identified as candidate predictive biomarker [55]  Sym004: polyclonal anti-EGFR antibody mix –Activity in HNSCC, potentially effective after cetuximab failure [56]  ABT-414: EGFR antibody–drug conjugate –Phase II testing [57] 53. Abdul Razak AR, et al. Ann Oncol. 2013;24:761-769. 54. ClinicalTrials.gov. NCT01577173. 55. Cervantes-Ruiperez A, et al. ASCO 2012. Abstract 2568. 56. Machiels JP, et al. ASCO 2013. Abstract 6002. 57. ClinicalTrials.gov. NCT01741727.

27. Emerging Novel Targets for HNSCC

28. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Receptor Tyrosine Kinases PI3K TSG HPV+ (n = 35)HPV- (n = 244) 58. Hayes DN, et al. ASCO 2013 Clinical Science Symposium. Abstract 6009. EGFR FGFR1 ERBB2 IGF1R EPHA2 DDR2 FGFR2 FGFR3 MET CCND1 MYC HRAS PIK3CA PTEN PIK3R1 NF1 TP53 CDKN2A 16% 10% 5% 4% 3% 2% 30% 14% 5% 18% 12% 1% 3% 82% 58% 6% 0% 3% 0% 3% 6% 0% 11% 0% 3% 0% 37% 6% 3% 0% 3% 0% Oncogenes The Cancer Genome Atlas (TCGA): Candidate Therapeutic Targets Amplification Homozygous deletion Mutation RPPA downregulation RPPA upregulation FGFR3-TACC3 fusion EGFRvIII MET exon 14 skipping

29. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma 60. Keck MK, et al. ASCO 2013. Abstract 6010. 12% 0% EGFR FGFR1 8% 0% FGFR2 0% 4% 0% 14% FGFR3 EPHA2 3% 4% DDR2 5% 2% 5% NF1/2 5% 11% RAS 10% 22% PIK3CA PIK3R1 3% 0% AKT 5% 2% 5% PTEN TSC 1/2 5% 8% Targetable Genetic Changes in HNSCC Oncogene Tumor Supressor Gene HPV- incidence HPV+ incidence MAPK pathway activation PI3K-AKT pathway activation SRC and STAT pathway activation mTOR

30. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Drugs in Development for HNSCC  PI3K pathway –BKM120 + cetuximab (phase II) –BYL719 + cetuximab (phase II) –Temsirolimus + cetuximab (phase II) –Rigosertib + cetuximab (phase II) –GDC-0980 (phase I HNSCC expansion cohort)  MET pathway –Tivantinib + cetuximab (phase II) –Ficlatuzumab + cetuximab (phase II)  EGFR/HER3 pathway –Afatinib + cetuximab ± paclitaxel (phase II) –LJM716 (phase I)  PD-1/PD-L1 immune checkpoints –MK3475 (phase I/II) –Expansion cohort of other PD-1/ PD-L1 agents  FGFR pathway –BGJ398 (phase II)  CDK4/6–cell cycle pathway –Palbociclib (phase I) –LEE011 (phase I)

31. clinicaloptions.com/oncology Treatment of Metastatic Head and Neck Squamous Cell Carcinoma Conclusions  HNSCC is the 6 th most common malignancy worldwide, and treatment options remain an unmet needs for patients with this disease  EGFR has been shown to be effect target for treatment; additional EGFR targeted agents in development  Evolving understanding of genetic profiling in patients with HNSCC may allow for development of additional targeted therapy –Promising new targets include: PI3K, FGFR, CCND1, PD1/PD-L1

32. Go Online for More CCO Coverage of HNSCC and Other Squamous Cell Carcinomas! Capsule Summaries of all the key data Additional CME-certified programs on HNSCC and other squamous cell carcinomas with expert faculty insights clinicaloptions.com/oncology