BACKGROUND: Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. PATIENTS AND METHODS: CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). RESULTS: Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. CONCLUSION: Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.
- Spigel, D. R.
- Vicente, D.
- Ciuleanu, T. E.
- Gettinger, S.
- Peters, S.
- Horn, L.
- Audigier-Valette, C.
- Pardo Aranda, N.
- Juan-Vidal, O.
- Cheng, Y.
- Zhang, H.
- Shi, M.
- Luft, A.
- Wolf, J.
- Antonia, S.
- Nakagawa, K.
- Fairchild, J.
- Baudelet, C.
- Pandya, D.
- Doshi, P.
- Chang, H.
- Reck, M.
Keywords
- Antineoplastic Combined Chemotherapy Protocols
- Humans
- *Lung Neoplasms/drug therapy
- Neoplasm Recurrence, Local/drug therapy
- Nivolumab/adverse effects
- Progression-Free Survival
- *Small Cell Lung Carcinoma/drug therapy
- *pd-1
- *biomarkers
- *immunotherapy
- *small-cell lung cancer
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- Daiichi Sankyo, Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, Janssen,
- Merck, Novartis, Seattle Genetics, Spectrum Pharmaceuticals, and Takeda. DV:
- honoraria: AstraZeneca
- consulting or advisory role: AstraZeneca, Bristol Myers
- Squibb, Merck Sharp & Dohme, Pfizer, Roche
- travel, accommodations, expenses:
- AstraZeneca. TEC: consulting or advisory role: A&D Pharma, Amgen, Astellas Pharma,
- AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Genentech/Roche,
- Janssen, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, Sanofi,
- Servier
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- advisory role: Bristol Myers Squibb, Nektar
- research funding: Bristol Myers Squibb
- (Inst), Genentech/Roche (Inst), Iovance Biotherapeutics (Inst). SP:
- consultation/advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, BioInvent,
- Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi
- Sankyo, Debiopharm, Eli Lilly, Foundation Medicine, Illumina, Janssen, Merck Sharp &
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- Xcovery
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- CA-V: consulting or advisory role: AbbVie, AstraZeneca, Boehringer Ingelheim,
- Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Takeda
- travel, accommodations,
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- Sharp & Dohme, Roche, Takeda. NPA: Consulting or advisory role: Merck Sharp & Dohme,
- Pfizer, Roche
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- honoraria: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Genentech/Roche,
- Merck Sharp & Dohme
- consulting or advisory role: AbbVie, AstraZeneca, Boehringer
- Ingelheim, Bristol Myers Squibb, Eli Lilly, Genentech/Roche, Merck Sharp & Dohme,
- Pfizer, Takeda
- travel, accommodations, expenses: Merck Sharp & Dohme, Roche. MS:
- speaker's bureau: Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research,
- Nanjing Medical University Affiliated Cancer Hospital. JW: honoraria: AbbVie, Amgen,
- AstraZeneca, Blueprint, Bristol Myers Squibb, Boehringer Ingelheim, Chugai, Eli
- Lilly, Ignyta, Janssen, Loxo, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda
- research funding: Bristol Myers Squibb, Johnson and Johnson, Novartis, Pfizer. SA:
- consulting or advisory role: Achilles Therapeutics, Amgen, AstraZeneca, Bristol
- Myers Squibb, Cellular Biomedicine Group, Celsius, GlaxoSmithKline, Memgen, Merck,
- RAPT Therapeutics, Samyang Biopharm, Venn Therapeutics
- travel, accommodations,
- expenses: Achilles Therapeutics, Amgen, Bristol Myers Squibb, Celsius,
- GlaxoSmithKline, Merck, RAPT Therapeutics. KN: honoraria: Astellas Pharma,
- AstraZeneca K.K., Bristol Myers Squibb, Carenet Health, Inc., Chugai Pharmaceutical
- Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Hisamitsu Pharmaceutical
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- employment: Bristol Myers Squibb, former employee of Johnson and Johnson. HC
- employment: Bristol Myers Squibb. MR: consulting or advisory role: AbbVie, Amgen,
- Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Merck, Merck Sharp &
- Dohme, Novartis, Pfizer, Roche, Takeda
- speaker's bureau: AbbVie, Amgen, Boehringer
- Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Merck, Merck Sharp & Dohme,
- Novartis, Pfizer, Roche, Takeda
- research funding: Boehringer Ingelheim, Bristol
- Myers Squibb
- travel, accommodations, expenses: AbbVie, Amgen, Boehringer Ingelheim,
- Bristol Myers Squibb, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer,
- Roche, Takeda. All other authors have declared no conflicts of interest. Data
- sharing Bristol Myers Squibb policy on data sharing may be found at
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