KEYNOTE-024: Extended Survival Outcomes With First-line Pembrolizumab in PD-L1+ NSCLC CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois *Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals NSCLC, non-small-cell lung cancer. This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

KEYNOTE-024: Background Pembrolizumab approvals for advanced NSCLC Monotherapy for treatment-naive and previously treated, PD-L1–positive disease Combination with pemetrexed + carboplatin for treatment-naive, nonsquamous NSCLC[1,2] KEYNOTE-024: first-line pembrolizumab significantly prolonged PFS and OS, improved ORR, with fewer treatment-related AEs vs platinum-based chemotherapy in PD-L1–positive (≥ 50%) advanced NSCLC[1] Current analysis updated OS and evaluated PFS2 (time from randomization to progression on second-line therapy or death)[3] PFS2 recommended to examine effect of crossover on OS and effect of first-line treatment on efficacy of subsequent regimen[4,5] AE, adverse event; NSCLC, non-small-cell lung cancer. 1. Reck M, et al. N Engl J Med. 2016;375:1823-1833. 2. Pembrolizumab [package insert]. 2017. 3. Brahmer JR, et al. ASCO 2017. Abstract 9000. 4. EMA. Evaluation of anticancer medicinal products in man. November 2013. 5. Dimopoulos MA, et al. Haematologica. 2015;100:e328-e330. Slide credit: clinicaloptions.com

KEYNOTE-024: Study Design Randomized, open-label phase III trial Stratified by ECOG PS (0 vs 1), histology (squamous vs nonsquamous), enrollment region Pts with untreated stage IV NSCLC, PD-L1 TPS ≥ 50%, ECOG PS 0/1, no activating EGFR mutation/ALK translocation, no active autoimmune disease needing systemic treatment, no untreated brain metastases (N = 305) Pembrolizumab 200 mg IV Q3W for up to 2 yrs (n = 154) Until PD or unacceptable toxicity Until PD; crossover allowed to pembrolizumab for up to 2 yrs after BICR-confirmed PD and safety criteria met Platinum-Doublet CT* for 4-6 cycles (n = 151) *Investigator’s choice of: pem + carb; pem + cis; pac + carb; gem + carb; gem + cis. Pem-containing regimens only for nonsquamous histology; these pts could receive pem maintenance treatment. BICR, blinded independent central review; carb, carboplatin; cis, cisplatin; CT, chemotherapy; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; f/u, follow-up; gem, gemcitabine; NSCLC, non-small-cell lung cancer; pac, paclitaxel; PD, progressive disease; pem, pemetrexed; PFS, progression-free survival; PFS2, PFS with ≥ 1 subsequent line following study treatment; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumor; TPS, tumor proportion score. Primary analysis endpoints (median f/u: 11.2 mos) Primary: PFS per RECIST v1.1 (BICR) Secondary: OS, ORR, safety Exploratory: DoR, PFS2 Slide credit: clinicaloptions.com Brahmer JR, et al. ASCO 2017. Abstract 9000. Reck M, et al. N Engl J Med. 2016;375:1823-1833.

KEYNOTE-024: Baseline Characteristics Pembrolizumab (n = 154) Chemotherapy (n = 151) Median age, yrs (range) 64.5 (33.0-90.0) 66.0 (38.0-85.0) Male, n (%) 92 (59.7) 95 (62.9) ECOG PS 1, n (%) 99 (64.3) 98 (64.9) Squamous histology, n (%) 29 (18.8) 27 (17.9) Current/former smoker, n (%) 149 (96.8) 132 (87.4) Metastases, n (%) Brain Liver 18 (11.7) 20 (13.0) 10 (6.6) 36 (23.8) Prior treatment, n (%) Neoadjuvant Adjuvant Radiation 3 (1.9) 6 (3.9) 35 (22.7) 1 (0.7) 3 (2.0) 43 (28.5) ECOG, Eastern Cooperative Oncology Group; PS, performance status. Slide credit: clinicaloptions.com Brahmer JR, et al. ASCO 2017. Abstract 9000.

KEYNOTE-024: Pt Disposition With Extended Follow-up Median follow-up: 19.1 mos (range: 14.3-27.6 mos) Characteristic Pembrolizumab (n = 154) Chemotherapy (n = 151) Treatment status, n Ongoing Completed Discontinued Received pemetrexed maintenance 46 1 107 N/A 29 120 Median first-line treatment duration, mos (range) 7.9 (1 day to 23.5+ mos) 3.5 (1 day to 22.9 mos) Effective crossover rate (ITT), % Crossed over to pembrolizumab, n Treated with anti–PD-1 outside of crossover, n 60.3 79 12 Any subsequent treatment, n Of ITT population, % Of discontinuations, % 48 31.2 44.9 97 64.2 80.8 Median second-line tx duration (range), mos 3.6 (1 day to 10.7+ mos) 3.5 (1 day to 20.3+ mos) ITT, intent to treat; mos, months; N/A, not applicable. Slide credit: clinicaloptions.com Brahmer JR, et al. ASCO 2017. Abstract 9000.

KEYNOTE-024: Second-line Systemic Tx Use Subsequent Tx, n (%) Pembrolizumab Arm (n = 48) Platinum doublet Carb + pem ± bevacizumab* Carb + pac ± bevacizumab† Carb + gem Cis + pem Cis + gem Plat + pem 42 (87.5) 17 (35.4) 9 (18.8) 8 (16.7) 5 (10.4) 2 (4.2) 1 (2.1) Platinum doublet median tx duration, mos (range) 3.6 (1 d to 10.7+ mos) Other Cis Cabozantinib Carb Cytarabine Pem + bevacizumab 6 (12.5) Nonplatinum doublet median tx duration, mos (range) 2.8 (1 d to 10.0+ mos) Subsequent Tx, n (%) Chemotherapy Arm (n = 97) Crossover to pembrolizumab Median tx duration, mos (range) 79 (81.4) 4.2 (1 day to 20.3+ mos) Anti–PD-1 outside of crossover Nivolumab Pembrolizumab 12 (12.4) 9 (9.3) 3 (3.1) Anti–PD-1 outside of crossover median tx duration, mos (range) 3.0 (1 day to 11.3+ mos) Other Pem Carb + gem Carb + pac Doc Pac 6 (6.2) 2 (2.1) 1 (1.0) Other median tx duration, mos (range) 1.9 (1 day to 5.2 mos) carb, carboplatin; cis, cisplatin; doc, docetaxel; gem, gemcitabine; pac, paclitaxel; pem, pemetrexed; plat, platinum; tx, treatment. *1 pt received bevacizumab. †3 pts received bevacizumab. Slide credit: clinicaloptions.com Brahmer JR, et al. ASCO 2017. Abstract 9000.

KEYNOTE-024: PFS2 Pembrolizumab (n = 154) Chemotherapy (n = 151) Median PFS2 (95% CI), mos 18.3 (12.7-NE) 8.4 (6.8-9.8) HR (95% CI) 0.54 (0.40-0.72); P < .001 Mos Pts at Risk, n 100 90 80 70 60 50 40 30 20 10 PFS2 (%) 6 3 9 12 18 15 21 24 154 151 134 121 112 99 96 64 90 56 71 36 40 18 16 6 3 1 59.7% 38.5% 51.0% 24.6% NE, not estimable; NR, not reached; PFS2, PFS with ≥ 1 subsequent line following study treatment. Slide credit: clinicaloptions.com Brahmer JR, et al. ASCO 2017. Abstract 9000. Reproduced with permission.

KEYNOTE-024: OS Pembrolizumab (n = 154) Chemotherapy (n = 151) Median OS (95% CI), mos NR (19.4-NE) 14.5 (9.8-19.6) HR (95% CI) 0.63 (0.46-0.88); P = .003 100 90 70.3% 54.8% 80 61.0% 43.0% 70 60 OS (%) 50 40 30 20 NE, not estimable; NR, not reached. 10 3 6 9 12 15 18 21 24 Pts at Risk, n Mos 154 151 136 123 121 107 112 88 106 79 88 64 57 35 20 15 4 4 Slide credit: clinicaloptions.com Brahmer JR, et al. ASCO 2017. Abstract 9000. Reproduced with permission.

KEYNOTE-024: Conclusions With longer follow-up, first-line pembrolizumab demonstrated continued OS benefit vs platinum-based chemotherapy in pts with PD-L1–positive advanced NSCLC Median OS: NR vs 14.5 mos (HR: 0.63; P = .003) OS curves remained separated even with effective crossover rate of 60% PFS2 significantly prolonged for pts allocated to first-line pembrolizumab vs chemotherapy Median PFS2: 18.3 vs 8.4 mos (HR: 0.54; P < .001) Investigators concluded that first-line pembrolizumab should be standard of care for NSCLC pts with tumors having PD-L1 TPS ≥ 50% due to prolonged survival and improved safety profile vs platinum-doublet chemotherapy NR, not reached; NSCLC, non-small-cell lung cancer; PFS2, PFS with ≥ 1 subsequent line following study treatment; TPS, tumor proportion score. Slide credit: clinicaloptions.com Brahmer JR, et al. ASCO 2017. Abstract 9000.

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