Long-term data comparing outcomes with immune checkpoint inhibitors versus chemotherapy in NSCLC are limited. The phase 3 trials CheckMate 017 and 057 demonstrated improved overall survival (OS), objective response rates (ORR), and quality of life, as well as a favorable safety profile, with the anti-programmed death (PD)-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous and non-squamous NSCLC, respectively. Updated results based on a minimum follow-up of 3 y are reported.
Patients were randomized 1:1 to receive nivolumab 3 mg/kg Q2W (with option to change to 480 mg Q4W after Sep 2016) or docetaxel 75 mg/m2 Q3W until progression or discontinuation. After completion of the primary analyses, patients who ended treatment with docetaxel could cross over to receive nivolumab. The primary endpoint of each study was OS; other endpoints were ORR, progression-free survival, and efficacy by PD ligand 1 (PD-L1) expression.
After a minimum follow-up of 36.6 mo in each study (Feb 2017 database locks), 6% of the 427 total patients randomized to the 2 nivolumab arms remained on treatment; no patients remained on docetaxel. Nivolumab continued to show an OS benefit versus docetaxel, with 3-y OS rates of 16% versus 6% in CheckMate 017 and 18% versus 9% in CheckMate 057. Similar to prior reports, an OS benefit was observed in squamous NSCLC regardless of PD-L1 expression, and in non-squamous NSCLC was enhanced at higher PD-L1 expression levels (Table). Of 427 patients in the combined nivolumab arms, 71 (17%) had OS ≥ 3 y. Additional 3-y data across trial endpoints will be presented.Table:
|OSa overall and by PD-L1 expression level||CheckMate 017||CheckMate 057|
|(squamous NSCLC)||(non-squamous NSCLC)|
|Nivolumab||Docetaxel||HR (95% CI)||Nivolumab||Docetaxel||HR (95% CI)|
|3-y OS rate, %||16||6||0.62 (0.48, 0.80)||18||9||0.74 (0.62, 0.89)|
With ≥3 y of follow-up from 2 randomized phase 3 studies, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced squamous and non-squamous NSCLC. Overall, 3-y survival was achieved in 17% of nivolumab-treated patients.
Clinical trial identification
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E. Felip Font: Member of advisory boards fro Eli Lilly, Pfizer, Roche, Merck Sharp & Dohme, Boehringre Ingelheim. Speaker\'s bureau/lecture fees from Astra Zeneca, Bristol-Myers Squibb and Novartis. S.N. Gettinger: Research funding: ARIAD, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Genentech, Incyte, Pfizer; Consulting fees: ARIAD, Bristol-Myers Squibb, Janssen. S.J. Antonia: Other from Bristol-Meyers Squibb, other from Novartis, other from Merck, other from CBMG, other from Boehringer Ingelheim, other from Genentech, other from AstraZeneca/MedImmune, other from Memgen, outside the submitted work. D.R. Spigel: Consulting/advisory roles & research funding from Genentech/Roche, Novartis, Celgene, BMS, Lilly, AstraZeneca, Pfizer, Clovis Oncology, BI research funding from Peregrine Pharma, Oncogenex, OncoMed, Amgen, Verastem, Daiichi Sankyo, Merck. O. Arrieta: Personal fees from Bristol-Myers Squibb. O. Aren Frontera: Personal fees for advisory boards with Bristol-Myers Squibb and Roche. J. Brahmer: Advisor/consultant for BMS (uncompensated), Celgene, Eli Lilly, Merck & Co, Syndax and has received grant/trial funding from BMS, Merck & Co, MedImmune/AstraZeneca, Johnson & Johnson, Incyte, Five Prime Therapeutics. L.Q. Chow: Grants and personal fees from BMS, during the conduct of the study; grants and/or personal fees from Novartis, BMS, Merck, Eli Lilly/Imclone, Genentech, Pfizer, AstraZeneca/MedImmune, Incyte, Seattle Genetics, Sanofi Genzyme, Amgen. L. Crinò: Personal fees from an advisory board for Bristol-Myers Squibb. C. Butts: Honoraria for participation in Advisory Boards from BMS, AstraZeneca, Pfizer and Merck. Participated in clinical trials sponsored by these, as well as Roche, BI, Novartis, and Lilly. No compensation for the participation. L. Horn: Personal fees from AbbVie, Genentech, Merck, Lilly, non-financial support from Bristol-Myers Squibb, non-financial support from Xcovery, non-financial support from Bayer. W.J. Geese, A. Li: Employee of Bristol-Myers Squibb. D. Healey: Other from Bristol-Myers Squibb, during the conduct of the study; other from Bristol-Myers Squibb, outside the submitted work. E.E. Vokes: Consultant/advisory role for AbbVie, Amgen, AstraZeneca, BMS, BI, Celegene, Eli Lilly, Genentech, Leidos, Merck, Regeneron, Serono, Takeda, VentiRx. All other authors have declared no conflicts of interest.