Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L)

• Published in: Journal for immunotherapy of cancer Vol. 8; no. 1; p. e000350
• Main Authors: Kato, Ryoji, Hayashi, Hidetoshi, Chiba, Yasutaka, Miyawaki, Eriko, Shimizu, Junichi, Ozaki, Tomohiro, Fujimoto, Daichi, Toyozawa, Ryo, Nakamura, Atsushi, Kozuki, Toshiyuki, Tanaka, Kentaro, Teraoka, Shunsuke, Usui, Kazuhiro, Nishino, Kazumi, Hataji, Osamu, Ota, Keiichi, Ebi, Noriyuki, Saeki, Sho, Akazawa, Yuki, Okuno, Motoyasu, Yamamoto, Nobuyuki, Nakagawa, Kazuhiko
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01-02-2020; BMJ Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Bias; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - mortality; Chemotherapy; Clinical/Translational Cancer Immunotherapy; Computer centers; Cytotoxicity; Docetaxel - pharmacology; Docetaxel - therapeutic use; Drug Combinations; Drug Synergism; Female; Histology; Humans; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Kaplan-Meier Estimate; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Male; Metastasis; Middle Aged; Mutation; Oxonic Acid - pharmacology; Oxonic Acid - therapeutic use; Patients; Pemetrexed - pharmacology; Pemetrexed - therapeutic use; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Progression-Free Survival; Propensity Score; Radiation therapy; Ramucirumab; Retrospective Studies; Statistical analysis; Tegafur - pharmacology; Tegafur - therapeutic use; Japan; non–small cell lung cancer; PD-1 inhibitors; chemotherapy; response; propensity score
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2019-000350

BackgroundStudies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response for non–small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of chemotherapy after PD-1 inhibitor treatment (CAP) compared with chemotherapy alone.MethodsWe conducted a retrospective observational cohort study for patients treated at 47 institutions across Japan between April 1, 2014 and July 31, 2017. Eligible patients had advanced or recurrent NSCLC who have undergone chemotherapy. Patients subsequently treated with chemotherapy (docetaxel with or without ramucirumab, S-1 or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort) were included. The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors.ResultsA total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics—including age, histology, EGFR or ALK genetic alterations, and brain metastasis—differed significantly between the two cohorts. After adjustment for patient characteristics with the IPW method, ORR was 18.9% for the CAP cohort and 11.0% for the control cohort (ORR ratio 1.71; 95% CI 1.19 to 2.46; p=0.004). IPW-adjusted Kaplan-Meier curves showed that median progression-free survival (PFS) for the CAP and control cohorts was 2.8 and 2.7 months (IPW-adjusted HR 0.95; 95% CI 0.80 to 1.12; p=0.55), and median overall survival (OS) was 9.2 and 10.4 months (IPW-adjusted HR 1.05; 95% CI 0.86 to 1.28; p=0.63), respectively.ConclusionsAfter accounting for selection bias by propensity score analysis, CAP showed a significantly higher ORR compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into a PFS or OS advantage, suggesting that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.