IFCT-1502 CLINIVO: real-world evidence of long-term survival with nivolumab in a nationwide cohort of patients with advanced non-small-cell lung cancer

O Molinier, B Besse, F Barlesi, C Audigier-Valette, S Friard, I Monnet, G Jeannin, J Mazières, J Cadranel, J Hureaux, W Hilgers, E Quoix, B Coudert, D Moro-Sibilot, E Fauchon, V Westeel, P Brun, A Langlais, F Morin, P J Souquet, N Girard, O Molinier, B Besse, F Barlesi, C Audigier-Valette, S Friard, I Monnet, G Jeannin, J Mazières, J Cadranel, J Hureaux, W Hilgers, E Quoix, B Coudert, D Moro-Sibilot, E Fauchon, V Westeel, P Brun, A Langlais, F Morin, P J Souquet, N Girard

Abstract

Background: Immunotherapy using inhibitors targeting immune checkpoint programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) is currently the standard of care in patients with advanced non-small-cell lung cancer (NSCLC).

Materials and methods: We carried out a nationwide cohort retrospective study of consecutive patients with advanced, refractory NSCLC who received nivolumab as second to later lines of treatment as part of the expanded access program. Key objectives were to assess the efficacy and safety of nivolumab and the efficacy of first post-nivolumab treatment.

Results: Nine hundred and two patients were enrolled: 317 (35%) with squamous cell carcinoma and 585 (65%) with non-squamous cell carcinoma. Median age was 64 years; there were 630 (70%) men, 795 (88%) smokers, 723 (81%) patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0/1, 197 (22%) patients with brain metastases, and 212 (27%) with liver metastases. Best response was partial response for 16.2% and stable disease (SD) for 30.5%. Progression-free survival and overall survival (OS) rates at 2, 3, and 5 years were 8% and 25%, 6% and 16%, and 4% and 10%, respectively. At multivariate analysis, ECOG PS ≥2 [hazard ratio (HR) = 2.13, 95% confidence interval (95% CI) 1.78-2.55, P < 0.001], squamous histology (HR = 1.17, 95% CI 1.01-1.36, P = 0.04), and presence of central nervous system metastases (HR = 1.29, 95% CI 1.08-1.54, P = 0.005) were significantly associated with lower OS. Four hundred and ninety-two patients received at least one treatment after discontinuation of nivolumab, consisting of systemic therapies in 450 (91%). Radiation therapy was delivered to 118 (24%) patients.

Conclusion: The CLINIVO cohort represents the largest real-world evidence cohort with the use of immune checkpoint inhibitor in advanced, metastatic NSCLC after failure of first-line chemotherapy, with long-term follow-up and analysis of subsequent therapies. Our data confirm the efficacy of nivolumab in a cohort larger than that reported in landmark clinical trials and identify prognostic factors, which reinforces the need for accurate selection of patients for treatment with immune checkpoint inhibitors. Our data indicate that oligoprogression is frequent after nivolumab exposure and provide a unique insight into the long-term survival.

Keywords: chemotherapy; immunotherapy; lung cancer; non-small-cell lung cancer; real-life evidence; sequence.

Conflict of interest statement

Disclosure OM reports personal fees from AstraZeneca, Takeda, BMS, MSD, Novartis, and AMGEN. NG reports research/grant support from MSD, AstraZeneca, AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sivan, and Trizell, and consultative services for Bristol Myers Squibb, AstraZeneca, AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sanofi, and Sivan. BB reports grants from AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Inivata, Janssen, Onxeo, OSE Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, and Tolero Pharmaceuticals. FB reports personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, ß. Hoffmann-La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda. CA-V reports personal fees and non-financial support from Roche, BMS, MSD, AstraZeneca, AbbVie, Pfizer, and Takeda. SF reports support for attending meetings and/or travel from Boehringer Ingelheim France, BMS, Leo Pharma, Sandoz, and Novartis Pharma SAS. JM reports personal fees from Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Hengrui, BLUEPRINT, DAIICHI, and Novartis and grants from Roche, AstraZeneca, Pierre Fabre, and BMS. JC reports consulting fees from AstraZeneca, Boehringer Ingelheim, BMS, Jansen, MSD, Pfizer, Roche, and Takeda. WH reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from BMS and Astellas and support for attending meetings and/or travel from Astellas, Pfizer, and Janssen. DM-S reports grants or contracts from Roche, AstraZeneca, Amgen, AbbVie, Pfizer, Takeda, and Lilly; consulting fees from Roche, AstraZeneca, Amgen, AbbVie, Pfizer, Takeda, and Lilly; payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Roche, AstraZeneca, Amgen, AbbVie, Pfizer, Takeda, Lilly, and BMS; and support for attending meetings and/or travel from Roche, AstraZeneca, Amgen, AbbVie, Pfizer, Takeda, Lilly, and BMS. VW reports honoraria from Roche, AstraZeneca, BMS, and MSD and non-financial support from Roche and Pfizer. PJS reports consulting fees, support for attending meetings and/or travel, payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from BMS and participated on a data safety monitoring board or advisory board for BMS. The remaining authors have declared no conflicts of interest.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Overall survival (A) and progression-free survival (B) of the 902 patients enrolled in the French Cooperative Thoracic Intergroup (IFCT) 1502-CLINIVO study after initiation of nivolumab. CI, confidence interval.
Figure 2
Figure 2
Overall survival (OS) (A) and progression-free survival (PFS) (B) of the 492 patients enrolled in the French Cooperative Thoracic Intergroup (IFCT) 1502-CLINIVO study from the initiation of first post-nivolumab treatment. (C) Duration of nivolumab treatment (red line) and first post-nivolumab treatment (blue line). CI, confidence interval.
Figure 2
Figure 2
Overall survival (OS) (A) and progression-free survival (PFS) (B) of the 492 patients enrolled in the French Cooperative Thoracic Intergroup (IFCT) 1502-CLINIVO study from the initiation of first post-nivolumab treatment. (C) Duration of nivolumab treatment (red line) and first post-nivolumab treatment (blue line). CI, confidence interval.

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