Regimen selection for combined immunotherapy in non-small cell lung cancer with PD-L1 < 1%: a multicenter, retrospective study from Japan (SPIRAL-LT1)

Abstract This multicenter retrospective study at 22 centers in Japan using electronic medical record data aimed to compare the effectiveness and safety of CTLA-4 regimens (ipilimumab plus nivolumab with or without chemotherapy) versus non-CTLA-4 regimens (pembrolizumab or atezolizumab plus chemotherapy) as first-line treatment for patients with advanced or recurrent NSCLC expressing PD-L1 < 1%. Dual primary endpoints were PFS and OS after propensity score matching (PSM) incorporating age, gender, PS, stage, histology, driver mutations, smoking, liver metastasis, and brain metastasis. Safety was assessed by the incidence and onset timing of ≥ grade 3 drug-related AEs. A total of 124 patients each were analyzed for both regimens. PFS and OS did not differ between CTLA-4 and non-CTLA-4 regimens, and exploratory subgroup analyses showed no substantial differences in treatment effect across patient characteristics. The CTLA-4 regimen had a higher incidence of ≥ grade 3 irAEs, particularly hepatic and gastrointestinal disease, and a lower incidence of ≥ grade 3 chemo-AEs. Onset of grade ≥ 3 irAEs also differed between regimens, and late-onset events with CTLA-4 regimens showed longer OS. In conclusion, while first-line CTLA-4 and non-CTLA-4 regimens showed comparable effectiveness in patients with NSCLC expressing PD-L1 < 1%, distinct toxicity profiles were observed, suggesting careful consideration of safety profiles is warranted.

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Journal
Scientific Reports
Published
2026-10-16
DOI
https://doi.org/10.1038/s41598-026-74087-1
Primary Topic
Cancer Immunotherapy and Biomarkers
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article
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article

Regimen selection for combined immunotherapy in non-small cell lung cancer with PD-L1 < 1%: a multicenter, retrospective study from Japan (SPIRAL-LT1)

Kohei Yoshimine, Yasuhiro Gotô, Kenta Murotani, Akira Nakao et al.
Scientific Reports
Cancer Immunotherapy and Biomarkers
article

Regimen selection for combined immunotherapy in non-small cell lung cancer with PD-L1 < 1%: a multicenter, retrospective study from Japan (SPIRAL-LT1)

Kohei Yoshimine, Yasuhiro Gotô, Kenta Murotani, Akira Nakao, Takayo Ota, Kosuke Hamai, Asuka Okada, Kazuhiro Ito, Toshiyuki Sumi, Tatsuya Imabayashi, Naoya Nishioka, Keiko Tanimura, Koichi Takayama, Koichi Azuma, Kenji Chibana, Makoto Hibino, Ryuichiro Takaki, Takashi Nomizo, Yuuya Nishii, Hiroyasu Kaneda, Tomohiro Oba, Kazuhiko Yamada, Kentaro Iwanaga, Yosuke Tamura, Daiki Murata, Tadaaki Yamada
article en

Abstract

Abstract This multicenter retrospective study at 22 centers in Japan using electronic medical record data aimed to compare the effectiveness and safety of CTLA-4 regimens (ipilimumab plus nivolumab with or without chemotherapy) versus non-CTLA-4 regimens (pembrolizumab or atezolizumab plus chemotherapy) as first-line treatment for patients with advanced or recurrent NSCLC expressing PD-L1 < 1%. Dual primary endpoints were PFS and OS after propensity score matching (PSM) incorporating age, gender, PS, stage, histology, driver mutations, smoking, liver metastasis, and brain metastasis. Safety was assessed by the incidence and onset timing of ≥ grade 3 drug-related AEs. A total of 124 patients each were analyzed for both regimens. PFS and OS did not differ between CTLA-4 and non-CTLA-4 regimens, and exploratory subgroup analyses showed no substantial differences in treatment effect across patient characteristics. The CTLA-4 regimen had a higher incidence of ≥ grade 3 irAEs, particularly hepatic and gastrointestinal disease, and a lower incidence of ≥ grade 3 chemo-AEs. Onset of grade ≥ 3 irAEs also differed between regimens, and late-onset events with CTLA-4 regimens showed longer OS. In conclusion, while first-line CTLA-4 and non-CTLA-4 regimens showed comparable effectiveness in patients with NSCLC expressing PD-L1 < 1%, distinct toxicity profiles were observed, suggesting careful consideration of safety profiles is warranted.

Scientific Reports
Kurume University (JP), Fujita Health University (JP), Osaka Medical and Pharmaceutical University (JP), Kyoto University (JP), National Kyushu Medical Center (JP), Kyoto Prefectural University of Medicine (JP), Fukuoka University Hospital (JP), Saga-Ken Medical Centre Koseikan (JP), Oita Prefectural Hospital (JP), Saiseikai Suita Hospital (JP), Kyoto first Red Cross hospital (JP), Izumi City General Hospital (JP), National Hospital Organization (JP), Aso Iizuka Hospital (JP), Saitama Red Cross Hospital (JP), Shin Koga Hospital (JP), Onomichi General Hospital (JP), Osaka Metropolitan University (JP), Shonan Fujisawa Tokusyukai Hospital (JP), Hakodate Goryoukaku Hospital (JP), Kyoto Yamashiro General Medical Center (JP), Fukuchiyama City Hospital (JP), Osaka Medical and Pharmaceutical University Hospital (JP), National Hospital Organization Okinawa Hospital (JP)
Good health and well-being
Openalex Percentile: Top 17%
Cancer Immunotherapy and Biomarkers
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