LBA3 Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (aNSCLC): CheckMate 227 - part 2 final analysis

Abstract

Abstract Background Immunotherapy with or without chemo has improved survival vs chemo in 1L aNSCLC. NIVO + chemo showed encouraging activity in a phase 1 study in this setting. CheckMate 227 is a multi-part, randomized, open-label, phase 3 study evaluating NIVO-based regimens vs chemo. We present final results from Part 2, which evaluated NIVO + chemo vs chemo in 1L aNSCLC. Methods Pts (N = 755) with chemo-naive, stage IV or recurrent NSCLC, ECOG PS 0–1, and no sensitizing EGFR/ALK alterations were randomized 1:1 to receive every 3 weeks NIVO 360 mg + chemo or chemo. Pts were stratified by histology (squamous [SQ] vs non-squamous [NSQ]), sex, and PD-L1 expression (< 1% vs ≥ 1%). Chemo was histology-based and continued for up to 4 cycles; pts with NSQ NSCLC could receive pemetrexed maintenance. Pts were treated until progression, unacceptable toxicity, or for 2 years for NIVO. The primary endpoint was overall survival (OS) with NIVO + chemo vs chemo in NSQ NSCLC. OS in all randomized pts (NSQ and SQ) was a secondary hierarchical endpoint. Results Baseline characteristics were generally balanced. Minimum follow-up was 19.5 mo. In pts with NSQ NSCLC, no statistically significant improvement in OS was seen with NIVO + chemo vs chemo (HR, 0.86 [95.62% CI, 0.69–1.08; P=0.1859]); median OS was 18.8 mo vs 15.6 mo; 12-mo OS rates were 67.3% vs 59.2%. HR for OS was 0.81 (95% CI, 0.67–0.97) in all randomized pts; 0.69 (95% CI, 0.50–0.97) in pts with SQ NSCLC. Progression-free survival and objective response rates favored NIVO + chemo in NSQ, SQ, and all randomized pts (table). Grade 3–4 tx-related adverse events occurred in 45% and 35% of all pts treated with NIVO + chemo and chemo, respectively.TableLBA3 Efficacy outcomes with 1L NIVO + chemo vs chemo in pts with NSQ NSCLC, SQ NSCLC, and in all randomized ptsTableNSQ NSCLCSQ NSCLCAll Randomized PtsNIVO + chemoChemoNIVO + chemoChemoNIVO + chemoChemon=270n = 273n=107n = 105n=377n = 378OSEvents, n (%)156 (57.8)164 (60.1)68 (63.6)75 (71.4)224 (59.4)239 (63.2)Median, mo18.815.618.312.018.314.7HR (95% CI)0.86 (0.69–1.08) a P = 0.18590.69 (0.50–0.97)0.81 (0.67–0.97)12-mo OS rate, %67.359.266.148.566.956.2PFSEvents, n (%)187 (69.3)200 (73.3)79 (73.8)82 (78.1)266 (70.6)282 (74.6)Median, mo8.75.87.14.48.45.5HR (95% CI)0.67 (0.55–0.82)0.51 (0.37–0.70)0.62 (0.52–0.73)12-mo PFS rate, %39.525.731.79.337.321.3Objective response rate, n (%)130 (48.1)80 (29.3)64 (59.8)34 (32.4)194 (51.5)114 (30.2)a95.62% CI Conclusion CheckMate 227 Part 2 did not meet the primary endpoint of OS for NIVO + chemo vs chemo in NSQ NSCLC. Descriptive analyses showed longer OS with NIVO + chemo in all randomized pts and SQ NSCLC. No new safety signals were observed. Clinical trial identification NCT02477826; Release date: June 23, 2015. Editorial acknowledgement Writing and editorial assistance was provided by Namiko Abe, PhD, of Caudex, funded by Bristol-Myers Squibb. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb. Disclosure L. Paz-Ares: Honoraria (self): Roche, MSD, Lilly, Novartis, Boehringer Ingelheim, AstraZeneca, Amgen, Sanofi, Pharmamar, Pfizer, Bristol-Myers Squibb, Merck, Takeda, Celgene, Servier, Sysmex, Incyte, Ipsen, Adacap, Bayer, Blueprint; Leadership role: Altum Sequencing; Research grant / Funding (institution): MSD, AstraZeneca, Pfizer, Bristol-Myers Squibb; Officer / Board of Directors: Genomica. T.E. Ciuleanu: Advisory / Consultancy: Astellas, Janssen, Bristol-Myers Squibb, Merck Serono, Amgen, Roche, Pfizer, Boehringer Ingelheim, Lilly, AstraZeneca, MSD, Sanofi, Novartis, Servier, AD Pharma. A. Pluzanski: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche; Speaker Bureau / Expert testimony: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Roche, Takeda; Travel / Accommodation / Expenses: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Roche. A. Nagrial: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche; Research grant / Funding (institution): Astra Zeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche. R. Kowalyszyn: Advisory / Consultancy: Astellas, Bristol-Myers Squibb, MSD; Speaker Bureau / Expert testimony: Bristol-Myers Squibb, MSD, Novartis; Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: Bristol-Myers Squibb, Lilly, MSD, Pfizer, Roche. C. Audigier-Valette: Honoraria (self): AbbVie, Pfizer; Honoraria (institution): Roche, MSD, Bristol-Myers Squibb, AstraZeneca; Advisory / Consultancy: Roche, MSD, Bristol-Myers Squibb, AstraZeneca, AbbVie, Pfizer. Y-L. Wu: Honoraria (self): AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche; Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche; Research grant / Funding (institution): AstraZeneca, Boehringer Ingelheim, BMS, Roche; Non-remunerated activity/ies: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche. H. Borghaei: Honoraria (self): University of Pennsylvania, CAR T Program, Takeda [Data and Safety Monitoring Board]; Advisory / Consultancy: Bristol-Myers Squibb, Lilly, Genentech, Celgene, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB, Amgen, AbbVie, Axiom, PharmaMar, Takeda, Huya Bio, GLG; Research grant / Funding (self): Millennium, Merck/Celgene, Bristol-Myers Squibb/Lilly. M.D. Hellmann: Advisory / Consultancy: Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, Janssen, Mirati, Syndax, Shattuck Labs, Immunai, Nektar, Blueprint Medicines; Research grant / Funding (institution): Bristol-Myers Squibb; Travel / Accommodation / Expenses: Bristol-Myers Squibb, AstraZeneca; Shareholder / Stockholder / Stock options: Shattuck Labs, Immunai. J. Brahmer: Advisory / Consultancy: Bristol-Myers Squibb, AstraZeneca, Genentech, Merck, Amgen. M. Reck: Honoraria (self): AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche; Advisory / Consultancy: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche. S. Ramalingam: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Roche/Genentech, Loxo, Tesaro, Merck, Daichi; Advisory / Consultancy: Amgen, AbbVie, Lilly, Genentech, Takeda; Research grant / Funding (institution): Bristol-Myers Squibb, Amgen, AstraZeneca, Takeda, Advaxis, Tesaro, Merck. L. Zhang: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD; Speaker Bureau / Expert testimony: AstraZeneca, Bristol-Myers Squibb, MSD, Roche; Research grant / Funding (institution): AstraZeneca, Bristol-Myers Squibb, Pfizer, Henrui Pharm. P. Bhagavatheeswaran: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. F.E. Nathan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. K.J. O'Byrne: Advisory / Consultancy: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim, Novartis, Teva, Janssen-Cilag, Natera; Speaker Bureau / Expert testimony: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim, Janssen-Cilag, Mundipharma; Travel / Accommodation / Expenses: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim; Shareholder / Stockholder / Stock options: Carp Pharmaceuticals, Carpe Vitae Phaemaceuticals; Licensing / Royalties: Various patents issues with licensee as listed. Queensland University of Technology and Trinity College Dublin. All other authors have declared no conflicts of interest.