Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis.

Background: First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.
Patients and Methods: Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor burden reduction in responders to nivolumab plus ipilimumab were also assessed.
Results: In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). Objective response rate was 36%; median duration of response was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor programmed death-ligand 1 (PD-L1) <1%, ≥1%, 1%-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor burden reduction ≥80%, 50% to <80%, or 30% to <50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population.
Conclusion: Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.
Competing Interests: Disclosure HB reports advisory/consulting fees, travel, accommodation, and expenses from Amgen, Bristol Myers Squibb, Genentech, Lilly, Merck, and Novartis; advisory/consulting fees from AbbVie, AstraZeneca, BioNTech AG, Boehringer Ingelheim, Cantargia AB, EMD Serono, Genmab, HUYA Bioscience International, Nuclaei, Pfizer, PharmaMar, Regeneron, Rgenix, Sonnet, Takeda, and Trovagene; honoraria from Amgen, Axiom Biotechnologies, Bristol Myers Squibb, Celgene, and Pfizer; research funding from Bristol Myers Squibb, Celgene, Lilly, Merck, and Millennium; stock interest with Nuclaei, Rgenix, and Sonnet; travel, accommodation, and expenses from Clovis Oncology; data safety monitoring board with Incyte and University of Pennsylvania; and ad boards with Guardant, Natera, and OncoCyte. TEC reports advisory/consulting fees, travel, accommodation, and expenses from Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Janssen, Merck Sharp & Dohme (MSD), Novartis/GlaxoSmithKline, Pfizer, Roche, Sanofi, and Servier. J-SL reports advisory/consulting fees from AstraZeneca and Ono Pharmaceutical. AP reports speaker fees, expert testimony, travel, accommodation, and expenses from Boehringer Ingelheim, Bristol Myers Squibb, and MSD; speaker fees and expert testimony from Roche, speaker fees from Pfizer; and speaker fees, travel, accommodation, and expenses from AstraZeneca. RBC reports advisory/consulting fees from AstraZeneca, Bristol Myers Squibb, MSD, Roche, and Takeda. MG reports advisory fees from Celularity and Guardant 360; and speaker fees from Guardant 360. YO reports advisory/consulting fees, honoraria, and research funding from AstraZeneca and Ono Pharmaceutical; and honoraria and research funding from Bristol Myers Squibb Japan. MN reports advisory/consulting fees, honoraria, and research funding from AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Lilly, MSD, Ono Pharmaceuticals, Taiho Pharmaceutical, and Takeda; advisory/consulting fees from AbbVie and Teijin Pharma; honoraria and research funding from Janssen, Merck, Novartis, and Pfizer; and honoraria from Boehringer Ingelheim and Nippon Kayaku. JG reports grant support from Advaxis, AstraZeneca, Bristol Myers Squibb, Genentech, Merck, and Pfizer; consulting and writing fees from Bristol Myers Squibb; and consulting fees from AstraZeneca, Genentech, and Pfizer. NR reports consulting fees and honoraria from AstraZeneca, Bristol Myers Squibb, G1 Therapeutics, Genentech, Merck, and Roche; research funding from Merck; honoraria from Novartis and Celgene; expert testimony fees from Bristol Myers Squibb and Celgene; speaker’s bureau fees from Bristol Myers Squibb; personal fees from AbbVie, Amgen, Jazz, Regeneron, and Sanofi; other fees from AbbVie; and a grant from Amgen. DRS reports grant support from Aeglea BioTherapeutics, Agios, Apollomics, Arcus, Arrys Therapeutics, Astellas Pharma, Bayer, BeiGene, BIND Therapeutics, BioNTech, Blueprint Medicine, Calithera, Celgene, Celldex, Clovis Oncology, Cyteir Therapeutics, Daiichi Sankyo, Denovo Biopharma, Eisai, Elevation Oncology, Eli Lilly, EMD Serono, Evelo, G1 Therapeutics, GlaxoSmithKline, GRAIL, Hutchinson MediPharma, ImClone Systems, ImmunoGen, Incyte, Ipsen, Janssen, Kronos Bio, Loxo Oncology, MacroGenics, MedImmune, Merck, Molecular Partners, Molecular Templates, Nektar, Neon Therapeutics, Novocure, Oncologie, PTC Therapeutics, PureTech Health, Razor Genomics, Repare Therapeutics, Rgenix, Takeda, Tesaro, Tizona Therapeutics, Transgene, University of Texas-Southwestern, and Verastem; and consulting support from Amgen, BeiGene, Curio Science, Eli Lilly, EMD Serono, Evidera, Exelixis, GlaxoSmithKline, Intellisphere, Janssen, Jazz Pharmaceuticals, Mirati Therapeutics, Molecular Templates, Novocure, Puma Biotechnology, Regeneron, and Sanofi-Aventis. SSR reports advisory/consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sanyo, Eisai, Genentech/Roche, GlaxoSmithKline, Lilly, Merck, Sanofi, Takeda; and research funding from Advaxis, AstraZeneca, Bristol Myers Squibb, EMD Serono, Genmab, GlaxoSmithKline, Merck, Takeda, Tesaro. LGPA reports travel, accommodation, and expenses from AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, and Takeda; honoraria from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Lilly, Merck Serono, Mirati, MSD, Novartis, Pfizer, PharmaMar, Roche/Genetech, Sanofi, Servier, and Takeda; speaker fees from Bristol Myers Squibb, Lilly, Merck Serono, MSD Oncology, Pfizer, and Roche/Genentech; research funding from AstraZeneca, Bristol Myers Squibb, MSD, PharmaMar; and personal fees from Altum Sequencing and Genomica. JFG reports consulting fees and honoraria from AstraZeneca, Blueprint, Bristol Myers Squibb, EMD Serono, Gilead, Glyde Bio, iTeos, Karyopharm, Loxo/Lilly, Merck, Moderna, Novartis, Oncorus, Pfizer, Regeneron, Silverback Therapeutics, and Takeda; grant support from Adaptimmune, Alexo, Array Biopharma, Blueprint, Bristol Myers Squibb, Jounce, Merck, Moderna, Novartis, and Tesaro; and an immediate family member who is an employee with equity at Ironwood Pharmaceuticals. MR reports advisory/consulting fees, travel, accommodation, and expenses from AbbVie and Amgen; advisory/consulting fees, speaker fees, expert testimony, travel, accommodation, and expenses from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Merck, MSD, Novartis, Pfizer, and Roche; and advisory/consulting fees from Samsung. MM reports advisory/consulting fees Alfasigma, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Incyte, iOnctura, Merck, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, and SciClone. KJO reports advisory/consulting fees, speaker fees, expert testimony, honoraria, travel, accommodation, and expenses from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Lilly Oncology, MSD, Pfizer, and Roche; advisory/consulting fees, speaker fees, expert testimony and honoraria from Novartis; advisory/consulting fees, speaker fees, and honoraria from Teva; advisory/consulting fees and honoraria from Natera, Takeda, Tristar, and Yuhan; and being a shareholder at Carpe Vitae Pharmaceuticals, DGC diagnostics, Foundation Medicine, and RepLuca Pharmaceuticals. AM reports employment and stock interest with Bristol Myers Squibb. FN reports employment at Bristol Myers Squibb; and ownership/stock interest with AstraZeneca, Johnson & Johnson, and Eli Lilly. PT reports employment and stock interest with Bristol Myers Squibb. MDH reports advisory/consulting fees from Achilles, Adagene, Adicet, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Da Volaterra, Eli Lilly, Genentech, Genzyme/Sanofi, Immunai, Instill Bio, Janssen, Mana Therapeutics, Merk, Mirati, Pact Pharma, Regeneron, Roche, and Shattuck Labs; research funding from Bristol Myers Squibb; stock interest with Arcus, Factorial, Immunai, and Shattuck Labs; a patent filed by Memorial Sloan Kettering related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208), which has received licensing fees from Personal Genome Diagnostics (PGDx); after the completion of this work, MDH began as an employee (and equity holder) at AstraZeneca. JRB reports advisory/consultancy fees and research funding from Bristol Myers Squibb; advisory/consultancy fees from Amgen, AstraZeneca, Genentech, GlaxoSmithKline, Merck, Regeneron, and Sanofi; consultancy fees and honoraria from Janssen; and advisory/consultancy fees and other from Roche/Genentech. SA has declared no conflicts of interest.
(Copyright © 2022. Published by Elsevier Ltd.)