Efficacy and safety of immune checkpoint inhibitor plus bevacizumab-based chemotherapy in advanced or recurrent KRAS-mutant non-squamous NSCLC: the SPIRAL-STONE study
11 affiliations
- 1Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
- 2Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, Kanagawa, Fujisawa, Japan
- 3Department of Respiratory Medicine, Shonan Oiso Hospital, Kanagawa, Oiso, Japan
- 4Department of Respiratory Medicine, Fukuchiyama City Hospital, Kyoto, Japan
- 5Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
- 6Department of Respiratory Medicine, Ichinomiya Nishi Hospital, Aichi, Ichinomiya, Japan
- 7Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Gunma, Japan
- 8Department of Respiratory Medicine, National Hospital Organization Omuta National Hospital, Omuta, Fukuoka, Japan
- 9Department of Breast Medical Oncology, Izumi City General Hospital, Izumi, Japan
- 10Department of Respiratory Medicine, Uji-Tokushukai Medical Center, Kyoto, Japan
- 11Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
Abstract
Introduction: Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung cancer is associated with a poor prognosis, underscoring the need for effective pharmacological treatments. An exploratory subgroup analysis of IMpower150 suggested potential clinical benefit of the atezolizumab-containing regimen in KRAS-mutant non-squamous NSCLC, although prospective data remain limited. We prospectively evaluated its efficacy and safety and performed exploratory biomarker analyses.
Methods: The study cohort comprised patients with advanced or recurrent KRAS-mutant non-squamous NSCLC scheduled to receive ICI plus bevacizumab-based chemotherapy at 10 Japanese institutions between January 2023 and December 2024. The primary endpoint was progression-free survival (PFS). Secondary endpoints included disease control rate (DCR), objective response rate (ORR), overall survival (OS), and safety. Associations between baseline serum levels of vascular endothelial growth factor (VEGF)-A and VEGF-D and treatment outcomes were explored in patients with available pretreatment samples.
Results: Of 22 enrolled patients, 21 received treatment and were analyzed for efficacy and safety; 17 were analyzed for serum biomarkers. All patients received atezolizumab, bevacizumab, carboplatin, and paclitaxel. The median PFS and OS were 6.0 and 17.1 months, respectively. Among 19 patients with measurable disease, the ORR was 42.1%, and the DCR was 68.4%. Grade ≥3 hematologic and non-hematologic adverse events occurred in 33.3% and 47.6% of patients, respectively. Baseline serum VEGF-A and VEGF-D levels were not significantly associated with the treatment outcomes.
Conclusions: ICI plus bevacizumab-based chemotherapy showed an ORR of 42.1%, a median PFS of 6.0 months, and a median OS of 17.1 months in patients with KRAS-mutant non-squamous NSCLC. Given the small sample size and single-arm design, these findings should be considered descriptive and hypothesis-generating. Pretreatment serum VEGF-A and VEGF-D levels were not significantly associated with clinical outcomes, although limited statistical power precludes definitive conclusions. Larger comparative studies with comprehensive molecular profiling are warranted.
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BibTeX
@article{ishida2026efficacy,
title = {{Efficacy and safety of immune checkpoint inhibitor plus bevacizumab-based chemotherapy in advanced or recurrent KRAS-mutant non-squamous NSCLC: the SPIRAL-STONE study}},
author = {Masaki Ishida and Tadaaki Yamada and Riko Kamada and Makoto Hibino and Masashi Egami and Takayuki Nakano and Tatsuya Imabayashi and Chieko Takumi and Koichi Ishida and Masafumi Takeshita and Ken Masubuchi and Miiru Izumi and Takayo Ota and Shoki Morito and Yusuke Chihara and Soichi Hirai and Shinsuke Shiotsu and Ryo Sawada and Hayato Kawachi and Naoya Nishioka and Masahiro Iwasaku and Koichi Takayama},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1875501},
url = {https://doi.org/10.3389/fimmu.2026.1875501},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Efficacy and safety of immune checkpoint inhibitor plus bevacizumab-based chemotherapy in advanced or recurrent KRAS-mutant non-squamous NSCLC: the SPIRAL-STONE study
AU - Masaki Ishida
AU - Tadaaki Yamada
AU - Riko Kamada
AU - Makoto Hibino
AU - Masashi Egami
AU - Takayuki Nakano
AU - Tatsuya Imabayashi
AU - Chieko Takumi
AU - Koichi Ishida
AU - Masafumi Takeshita
AU - Ken Masubuchi
AU - Miiru Izumi
AU - Takayo Ota
AU - Shoki Morito
AU - Yusuke Chihara
AU - Soichi Hirai
AU - Shinsuke Shiotsu
AU - Ryo Sawada
AU - Hayato Kawachi
AU - Naoya Nishioka
AU - Masahiro Iwasaku
AU - Koichi Takayama
PY - 2026
DA - 2026/10/12
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1875501
UR - https://doi.org/10.3389/fimmu.2026.1875501
AB - Introduction: Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung cancer is associated with a poor prognosis, underscoring the need for effective pharmacological treatments. An exploratory subgroup analysis of IMpower150 suggested potential clinical benefit of the atezolizumab-containing regimen in KRAS-mutant non-squamous NSCLC, although prospective data remain limited. We prospectively evaluated its efficacy and safety and performed exploratory biomarker analyses. Methods: The study cohort comprised patients with advanced or recurrent KRAS-mutant non-squamous NSCLC scheduled to receive ICI plus bevacizumab-based chemotherapy at 10 Japanese institutions between January 2023 and December 2024. The primary endpoint was progression-free survival (PFS). Secondary endpoints included disease control rate (DCR), objective response rate (ORR), overall survival (OS), and safety. Associations between baseline serum levels of vascular endothelial growth factor (VEGF)-A and VEGF-D and treatment outcomes were explored in patients with available pretreatment samples. Results: Of 22 enrolled patients, 21 received treatment and were analyzed for efficacy and safety; 17 were analyzed for serum biomarkers. All patients received atezolizumab, bevacizumab, carboplatin, and paclitaxel. The median PFS and OS were 6.0 and 17.1 months, respectively. Among 19 patients with measurable disease, the ORR was 42.1%, and the DCR was 68.4%. Grade ≥3 hematologic and non-hematologic adverse events occurred in 33.3% and 47.6% of patients, respectively. Baseline serum VEGF-A and VEGF-D levels were not significantly associated with the treatment outcomes. Conclusions: ICI plus bevacizumab-based chemotherapy showed an ORR of 42.1%, a median PFS of 6.0 months, and a median OS of 17.1 months in patients with KRAS-mutant non-squamous NSCLC. Given the small sample size and single-arm design, these findings should be considered descriptive and hypothesis-generating. Pretreatment serum VEGF-A and VEGF-D levels were not significantly associated with clinical outcomes, although limited statistical power precludes definitive conclusions. Larger comparative studies with comprehensive molecular profiling are warranted.
SN - 1664-3224
ER -