Nivolumab plus ipilimumab with chemotherapy for non-small cell lung cancer with untreated brain metastases: A multicenter single-arm phase 2 trial (NIke, LOGiK 2004)
- PMID: 39357279
- DOI: 10.1016/j.ejca.2024.115052
Nivolumab plus ipilimumab with chemotherapy for non-small cell lung cancer with untreated brain metastases: A multicenter single-arm phase 2 trial (NIke, LOGiK 2004)
Abstract
Background: The effect of dual immunotherapy combined with platinum-based chemotherapy on untreated brain metastases derived from non-small cell lung cancer (NSCLC) has remained unclear.
Methods: This multicenter single-arm phase 2 study enrolled patients with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥ 5 mm in size that had not been previously treated. Patients received nivolumab plus ipilimumab combined with platinum-doublet chemotherapy (two cycles), followed by nivolumab-ipilimumab alone. The primary endpoint of the study was intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥ 5 mm as target lesions.
Results: A total of 30 patients from 18 institutions was enrolled in this study. The median age was 66.5 years (range, 47-83 years), and 26 patients (87 %) had a non-squamous cell carcinoma histology. The median size of all target brain lesions was 8.4 mm, with a range of 5-39 mm. The intracranial response rate assessed by modified RECIST was 50.0 % (95 % CI, 33.2-66.8 %), with the rate of complete response being 20.0 %, and the study met its primary endpoint. The systemic response rate was 53.3 % (95 % CI, 36.1-69.8 %), and responses for intracranial and extracranial lesions were generally consistent. The median intracranial progression-free survival was 8.1 months, and both the median intracranial duration of response and time to brain radiotherapy were not reached.
Conclusion: Nivolumab plus ipilimumab combined with platinum-based chemotherapy showed promising intracranial activity in NSCLC patients with untreated brain metastases.
Trial registration: jRCT071210019.
Keywords: Immunotherapy; Nivolumab plus ipilimumab with chemotherapy; Non–small cell lung cancer (NSCLC); Untreated brain metastases.
Copyright © 2024 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Y Tsuchiya-Kawano has received personal fees from Bristol-Myers Squibb, Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Kyowa hakko Kirin, MSD, Ono Pharmaceutical, and Takeda Pharmaceutical outside the submitted work. Y Shiraishi has received grants and personal fees from Chugai Pharmaceutical as well as personal fees from Ono Pharmaceutical, Taiho Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, and Kyowa Kirin outside the submitted work. K Tanaka has received personal fees from Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, Takeda Pharmaceutical, Pfizer, MSD, Novartis, and Bristol-Myers Squibb outside the submitted work. M Tachihara has received grants from AstraZeneca, Chugai Pharmaceutical, and Eli Lilly as well as personal fees from Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, AstraZeneca, MSD, Novartis Pharmaceuticals, Takeda Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, Daiichi Sankyo, Pfizer, and Janssen Pharmaceutical outside the submitted work. T Okamoto has received grants from Chugai Pharmaceutical, AstraZeneca, Boehringer Ingelheim, MSD, Eli Lilly, and Bristol-Myers Squibb as well as personal fees from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Ono Pharmaceutical, MSD, Eli Lilly, and Bristol-Myers Squibb outside the submitted work. I Okamoto has received grants from Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD, Eli Lilly, Astellas, Bristol-Myers Squibb, Novartis, Pfizer, and AbbVie; consulting fees from AstraZeneca, Bristol-Myers Squibb, and AbbVie; and personal fees from AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Chugai Pharmaceutical, Ono Pharmaceutical, MSD, Eli Lilly, Bristol-Myers Squibb, Novartis, and Pfizer outside the submitted work. All other authors declare no competing interests.
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