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Randomized Controlled Trial
. 2024 Nov;25(7):e362-e368.
doi: 10.1016/j.cllc.2024.06.005. Epub 2024 Jun 29.

Treatment-Switching Adjustment of Overall Survival in CheckMate 227 Part 1 Evaluating First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy for Metastatic Nonsmall Cell Lung Cancer

Martin Reck  1 , Tuli De  2 , Luis Paz-Ares  3 , Mark Edmondson-Jones  2 , Yong Yuan  4 , Georgia Yates  5 , Roberto Zoffoli  6 , Mohammad Ashraf Chaudhary  7 , Adam Lee  8 , Nebibe Varol  8 , John R Penrod  7
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Free article
Randomized Controlled Trial

Treatment-Switching Adjustment of Overall Survival in CheckMate 227 Part 1 Evaluating First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy for Metastatic Nonsmall Cell Lung Cancer

Martin Reck et al. Clin Lung Cancer. 2024 Nov.
Free article

Abstract

Objectives: CheckMate 227 (NCT02477826) evaluated first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic nonsmall cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) expression ≥ 1% or < 1% and no EGFR/ALK alterations. However, many patients randomized to chemotherapy received subsequent immunotherapy. Here, overall survival (OS) and relative OS benefit of nivolumab-plus-ipilimumab were adjusted for potential bias introduced by treatment switching.

Materials and methods: Treatment-switching adjustment analyses were conducted following the NICE Decision Support Unit Technical Support Document 16, for CheckMate 227 Part 1 OS data from treated patients (database lock, July 2, 2019). Inverse probability of censoring weighting (IPCW) was used in the base-case analysis; other methods were explored as sensitivity analyses.

Results: Of 1166 randomized patients, 391 (PD-L1 ≥ 1%) and 185 (PD-L1 < 1%) patients received nivolumab-plus-ipilimumab; 387 (PD-L1 ≥ 1%) and 183 (PD-L1 < 1%) patients received chemotherapy, with 29.3-month minimum follow-up. Among chemotherapy-treated patients, 169/387 (43.7%; PD-L1 ≥ 1%) and 66/183 (36.1%; PD-L1 < 1%) switched to immunotherapy poststudy. Among treated patients, median OS was 17.4 months with nivolumab-plus-ipilimumab versus 14.9 months with chemotherapy (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.68-0.95) in the PD-L1 ≥ 1% subgroup and 17.1 versus 12.4 months (HR, 0.62; 95% CI, 0.49-0.80) in the PD-L1 < 1% subgroup. After treatment-switching adjustment using IPCW, the HR (95% CI) for OS for nivolumab-plus-ipilimumab versus chemotherapy was reduced to 0.68 (0.56-0.83; PD-L1 ≥ 1%) and 0.53 (0.40-0.69; PD-L1 < 1%). Sensitivity analyses supported the robustness of the results.

Conclusion: Treatment-switching adjustments resulted in a greater estimated relative OS benefit with first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic NSCLC.

Keywords: Anti-PD-1; Checkpoint inhibitor; Immunotherapy; Inverse probability of censoring weighting; NSCLC.

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Conflict of interest statement

Disclosure The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Martin Reck reports receiving consulting fees from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Lilly, Merck, Mirati, MSD, Novartis, Pfizer, Roche, Regeneron, Sanofi; honoraria from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Lilly, Merck, Mirati, MSD, Novartis, Pfizer, Roche, Regeneron, Sanofi; travel support for meetings from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Merck, Mirati, MSD, Lilly, Novartis, Pfizer, Roche, Regeneron, Sanofi; and Data Safety Monitoring Board or Advisory Board participation for Daiichi Sankyo and Sanofi. Luis Paz-Ares reports receiving leadership fees from ALTUM Sequencing and Genomica; honoraria from Amgen, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, GSK, Janssen, Lilly, Medscape, Merck Serono, Mirati Therapeutics, MSD, Novartis, Pfizer, PharmaMar, Regeneron, Roche, Sanofi, and Takeda; speaker's bureau fees from AstraZeneca, Bristol Myers Squibb, Lilly, Merck Serono, MSD Oncology, Pfizer, and Roche; and research funding to his institution from AstraZeneca, Bristol Myers Squibb, Kura Oncology, MSD, PharmaMar, and Pfizer. Tuli De, Mark Edmondson-Jones and Georgia Yates are employees of Paraxel which received consulting fees from Bristol Myers Squibb for the current work. Roberto Zoffoli reports receiving stock options as a former employee of Bristol Myers Squibb. Yong Yuan is an employee of Bristol Myers Squibb. Adam Lee, Mohammad Ashraf Chaudhary, Nebibe Varol, and John R. Penrod are employees of and have stock ownership in Bristol Myers Squibb. All authors received support for the present manuscript in the form of funding, medical writing, and article processing charges from Bristol Myers Squibb.

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