Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L)
Background Studies 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 e...
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
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| author | Nobuyuki Yamamoto Ryoji Kato Hidetoshi Hayashi Yasutaka Chiba Eriko Miyawaki Junichi Shimizu Tomohiro Ozaki Daichi Fujimoto Ryo Toyozawa Atsushi Nakamura Toshiyuki Kozuki Kentaro Tanaka Shunsuke Teraoka Kazuhiro Usui Kazumi Nishino Osamu Hataji Keiichi Ota Noriyuki Ebi Sho Saeki Yuki Akazawa Motoyasu Okuno Kazuhiko Nakagawa |
| author_facet | Nobuyuki Yamamoto Ryoji Kato Hidetoshi Hayashi Yasutaka Chiba Eriko Miyawaki Junichi Shimizu Tomohiro Ozaki Daichi Fujimoto Ryo Toyozawa Atsushi Nakamura Toshiyuki Kozuki Kentaro Tanaka Shunsuke Teraoka Kazuhiro Usui Kazumi Nishino Osamu Hataji Keiichi Ota Noriyuki Ebi Sho Saeki Yuki Akazawa Motoyasu Okuno Kazuhiko Nakagawa |
| author_sort | Nobuyuki Yamamoto |
| collection | DOAJ |
| description | Background Studies 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.Methods We 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.Results A 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.Conclusions After 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. |
| format | Article |
| id | doaj-art-a1e05f97528e462ca8d6640b3c0bea4b |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-a1e05f97528e462ca8d6640b3c0bea4b2024-11-09T05:10:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000350Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L)Nobuyuki Yamamoto0Ryoji Kato1Hidetoshi Hayashi2Yasutaka Chiba3Eriko Miyawaki4Junichi Shimizu5Tomohiro Ozaki6Daichi Fujimoto7Ryo Toyozawa8Atsushi Nakamura9Toshiyuki Kozuki10Kentaro Tanaka11Shunsuke Teraoka12Kazuhiro Usui13Kazumi Nishino14Osamu Hataji15Keiichi Ota16Noriyuki Ebi17Sho Saeki18Yuki Akazawa19Motoyasu Okuno20Kazuhiko Nakagawa21Internal Medicine III, Wakayama Medical University, Wakayama, Japan1 Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDepartment of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanClinical Research Center, Kindai University Hospital, Osaka, Japan3 Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan4 Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan5 Department of Medical Oncology, Kishiwada City Hospital, Kishiwada, JapanInternal Medicine Ⅲ, Wakayama Medical University, Wakayama, JapanDepartment of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan8 Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, JapanDepartment of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan10 Research Institute for Diseases of The Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan11 Third Department of Internal Medicine, Wakayama Medical University, Wakayama, JapanRespiratory Medicine, NTT Medical Center Tokyo, Tokyo, JapanDepartment of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan14 Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Japan15 Department of Respiratory Disease, National Hospital Organization Fukuoka Higashi Medical Center, Koga, Japan16 Department of Respiratory Medicine, Iizuka Hospital, Iizuka, Japan17 Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan18 Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan19 Department of Respiratory Medicine, Okazaki City Hospital, Okazaki, JapanDepartment of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanBackground Studies 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.Methods We 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.Results A 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.Conclusions After 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.https://jitc.bmj.com/content/8/1/e000350.full |
| spellingShingle | Nobuyuki Yamamoto Ryoji Kato Hidetoshi Hayashi Yasutaka Chiba Eriko Miyawaki Junichi Shimizu Tomohiro Ozaki Daichi Fujimoto Ryo Toyozawa Atsushi Nakamura Toshiyuki Kozuki Kentaro Tanaka Shunsuke Teraoka Kazuhiro Usui Kazumi Nishino Osamu Hataji Keiichi Ota Noriyuki Ebi Sho Saeki Yuki Akazawa Motoyasu Okuno Kazuhiko Nakagawa Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L) Journal for ImmunoTherapy of Cancer |
| title | Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L) |
| title_full | Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L) |
| title_fullStr | Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L) |
| title_full_unstemmed | Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L) |
| title_short | Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L) |
| title_sort | propensity score weighted analysis of chemotherapy after pd 1 inhibitors versus chemotherapy alone in patients with non small cell lung cancer wjog10217l |
| url | https://jitc.bmj.com/content/8/1/e000350.full |
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