Atezolizumab with carboplatin plus nab-paclitaxel combination therapy for advanced nonsquamous non-small cell lung cancer with impaired renal function: A multicenter, single-arm phase 2 trial (RESTART, LOGiK 2002)
- PMID: 40253945
- DOI: 10.1016/j.lungcan.2025.108543
Atezolizumab with carboplatin plus nab-paclitaxel combination therapy for advanced nonsquamous non-small cell lung cancer with impaired renal function: A multicenter, single-arm phase 2 trial (RESTART, LOGiK 2002)
Abstract
Background: The current standard of care for advanced non-small cell lung cancer (NSCLC) without driver oncogenes is platinum-based chemotherapy together with immune checkpoint inhibition. However, most phase 3 trials of such combination therapy have excluded patients with renal impairment, with prospective data on its efficacy and safety in such patients thus being limited.
Methods: This multicenter, single-arm phase 2 study enrolled chemotherapy-naïve individuals with advanced nonsquamous NSCLC and renal impairment defined as a creatinine clearance (CCr) of 15 to <45 mL/min. Patients received four cycles of atezolizumab in combination with carboplatin plus nab-paclitaxel, followed by atezolizumab alone. The primary endpoint of the study was objective response rate as determined by Response Evaluation Criteria in Solid Tumors.
Results: Twenty-five patients were enrolled from 13 centers. The median age was 78 years (range, 63-83 years). Median CCr was 38.0 mL/min (range, 19.0-44.3 mL/min). There were no treatment-related deaths or cases requiring hemodialysis. Worsening of chronic kidney disease to grade 4, defined as a CCr of <15 mL min-1 1.73 m-2, occurred in two patients (8 %), with the decreases in CCr being transient and both patients subsequently recovering. The objective response rate was 36.0 % (60 % confidence interval, 28.4-44.4 %), and the study did not meet its primary endpoint. Median progression-free survival and overall survival were 7.1 and 19.9 months, respectively.
Conclusions: Carboplatin plus nab-paclitaxel with atezolizumab is a potentially feasible treatment option for advanced nonsquamous NSCLC with renal impairment.
Keywords: Atezolizumab; Carboplatin; Immune checkpoint inhibitor; Nab-paclitaxel; Nonsquamous non–small cell lung cancer; Renal impairment.
Copyright © 2025 The Authors. Published by Elsevier B.V. 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: Yoshimasa Shiraishi received grants from Chugai Pharmaceutical and personal fees from Chugai Pharmaceutical, Ono Pharmaceutical, Taiho Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, and Kyowa Kirin outside the submitted work. Yukihiro Toi received personal fees from Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Chugai Pharmaceutical, AstraZeneca, and Taiho Pharmaceutical outside the submitted work. Kazushige Wakuda received grants from Chugai Pharmaceutical, AstraZeneca, Novartis, Abbvie, AMGEN, MSD, Daiichi Sankyo, and Dizal Pharma as well as personal fees from Chugai Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Ono Pharmaceutical, MSD, AstraZeneca, Daiichi Sankyo, Janssen Pharmaceutical, Takeda Pharmaceutical, and Nihon Kayaku outside the submitted work. Hirotaka Matsumoto received personal fees from AstraZeneca, Boehringer Ingelheim, Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, MSD, Nippon Kayaku, Kyowa Kirin, and Eli Lilly outside the submitted work. Hidetoshi Hayashi has received grants from IQVIA Services JAPAN, Eisai, SYNEOS HEALTH CLINICAL, EP-CRSU, EPS Corporation, Shionogi & Co, Nippon Kayaku, Otsuka Pharmaceutical, Takeda Pharmaceutical, GlaxoSmithKline, MSD, Sanofi, Amgen, Chugai Pharmaceutical, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, Bristol Myers Squibb, SRL Medisearch, Janssen Pharmaceutical, PRA Health Sciences, CMIC, Astellas Pharma, Pfizer R&D Japan G.K., Ascent Development Services, Labcorp Development Japan, Kobayashi Pharmaceutical, Bayer Yakuhin, Pfizer Japan, AstraZeneca, AbbVie, Daiichi Sankyo, A2 Healthcare Corp, Novartis Pharma, Eli Lilly Japan, Merck Biopharma, Medpace Japan, Kyowa Kirin, Japanese Gastric Cancer Association, Thoracic Oncology Research Group, Clinical Research Support Center Kyushu, West Japan Oncology Group, Japan Clinical Cancer Research Organization, Comprehensive Support Project for Oncological Research of Breast Cancer, EPS International, Mebix, Ono Pharmaceutical, Mochida Pharmaceutical, Covance Japan, Japan Clinical Research Operations, Medical Research Support as well as personal fees from Ono Pharmaceutical, Merck Biopharma, Daiichi Sankyo, 3H Clinical Trial, AstraZeneca, Novartis Pharma, Chugai Pharmaceutical, Bristol Myers Squibb, Eli Lilly Japan, Amgen, MSD, Sysmex Corporation, Pfizer Japan, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Janssen Pharmaceutical, and Guardant Health Japan, AbbVie, and Novocure outside the submitted work. Masahide Mori received personal fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi-Sankyo, Eli Lilly, Kyowa Kirin, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Takeda Pharmaceutical outside the submitted work. Shoichi Kuyama received personal fees from Chugai Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Pfizer, MSD, and Kyowa Kirin outside the submitted work. Haruki Kobayashi received grants from Taiho Pharmaceutical, Sanofi, Shanghai Haihe Pharmaceutical, MSD, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Inc, Eli Lilly, and Seagen Inc as well as personal fees from Chugai Pharmaceutical, Taiho Pharmaceutical, Ono Pharmaceutical, and Novartis outside the submitted work. Isamu 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 conflicts of interest.
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