Efficacy and Safety of Carboplatin With Nab-Paclitaxel Versus Docetaxel in Elderly Patients with Squamous-Cell Lung Cancer (CAPITAL): A Randomized, Multicenter, Open-Label, Phase III Trial

Background: In Japan, docetaxel, a cytotoxic monotherapy, is the standard drug administered to elderly patients with advanced non-small cell lung cancer (NSCLC). Carboplatin plus nab-paclitaxel (nab-PC) demonstrated a high objective response rate (ORR) in patients with squamous histology and was suggested to improve overall survival (OS) for these patients. The CAPITAL trial aimed to assess the safety and efficacy of nab-PC versus docetaxel as first-line therapy for elderly patients with advanced squamous NSCLC. Methods: This multicenter, open-label, phase III, randomized trial was performed at 92 institutions in Japan. Inclusion criteria: 1) advanced squamous NSCLC with no prior systemic chemotherapy, 2) age ≥70 years, and 3) Eastern Cooperative Oncology Group performance status 0 or 1. Patients were randomized 1:1 to nab-PC arm (carboplatin AUC, 6 mg/mL/min plus nab-paclitaxel 100 mg/m2 weekly) or D arm (docetaxel 60 mg/m2) for each 21-day cycle. Findings: The nab-PC arm showed higher OS (hazard ratio [HR]: 0·52; 90%CI: 0·38–0·70; median: 16·9 versus 10·9 months; p = 0·0003), progression-free survival (median: 5·8 versus 4·0 months; HR: 0·42; 95%CI: 0·30–0·58; p < 0·0001), and ORR (66·3 versus 28·0%; p < 0·0001) than the D arm. The most common grade 3 or 4 adverse events were leukopenia (46·3%), neutropenia (63·2%), and anemia (38·9%) in the nab-PC arm, and leukopenia (56·7%), neutropenia (77·3%), and febrile neutropenia (17·5%) in the D arm; ≥ grade 2 sensory peripheral neuropathy was observed in 15 (15·8%) and 1 (1·0%) patient(s) in the nab-PC and D arms, respectively. Serious treatment-related adverse events and deaths occurred in 13 (13·7%) and 11 (11·3%) patients and in 2 and 1 patient(s) in the nab-PC and D arms, respectively. Interpretation: Nab-PC improved OS more than docetaxel and can be used as standard first-line treatment for elderly patients with advanced squamous NSCLC. Clinical Trial Registration Details: This trial was registered with the UMIN Clinical Trials Registry (UMIN000019843) and the Japan Registry of Clinical Trials (jRCTs041180110) and its protocol has been published previously. Funding Information: This study was conducted by the National Hospital Organization Nagoya Medical Center under a funding contract with Taiho Pharmaceutical Co. Ltd., Tokyo, Japan. Declaration of Interests: Y.K. reports grants from Taiho Pharmaceutical, during the conduct of the study; grants and personal fees from MSD, personal fees from AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Boehringer Ingelheim, Ono pharmaceutical, outside the submitted work. S.I. reports grants and personal fees from ONO PHARMACEUTICAL CO., LTD., personal fees from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., MSD K.K, Bristol-Myers Squibb K.K., Taiho Pharmaceutical Co., Ltd., DAIICHI SANKYO COMPANY, LIMITED., outside the submitted work. H.S. reports grants from Taiho Pharmaceutical, during the conduct of the study; grants and personal fees from AstraZeneca, MSD K.K, Ono Pharmaceutical, personal fees from Boehringer Ingelheim, Chugai Pharma, from Kyorin, outside the submitted work. A.K. reports grants from Taiho Pharmaceutical Co., Ltd., during the conduct of the study; personal fees from Bayer Yakuhin, Ltd., outside the submitted work. S.A. reports grants from The National Cancer Center Research and Development Fund (26-A-22, 29-A-15, 2020-A-13), Taiho Pharmaceutical Co Ltd, during the conduct of the study; grants and personal fees from AstraZeneca, Ono, Taiho, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, MSD, Eli Lilly, Chugai, Merck, grants and non-financial support from F. Hoffmann-La Roche, personal fees from Hisamitsu, Kyowa Hakko Kirin, Novartis Pharma, Thermo Fisher Scientific, outside the submitted work.YT reports grants and personal fees from Taiho pharmaceutical Co, during the conduct of the study; grants and personal fees from Eli Lilly, Ono pharmaceutical Co, Chugai pharmaceutical Co, MSD, Takeda, grants from Daiichi Sankyo, Kyowa-Hakko Kirin, personal fees from Novartis, Boehringer Ingelheim, AstraZeneca, outside the submitted work. A.I. reports personal fees from AstraZeneca, Eli Lilly, Boehringer Ingelheim, Pfizer, Chugai Pharmaceutical, MSD, Daiichi Sankyo, outside the submitted work. T.K. reports personal fees from AstraZeneca, MSD, Eli Lilly, Chugai, Ono, Bristol Myers, Boehringer Ingelheim, grants from AstraZeneca, MSD, Ono, Eli Lilly, Takeda, outside the submitted work. I.O. reports grants from Boehringer Ingelheim, during the conduct of the study; grants and personal fees from AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD Oncology, Lilly, Bristol-Myers Squibb, Chugai Pharma, grants from Astellas Pharma, Novartis, AbbVie, personal fees from Pfizer, outside the submitted work. M.Y. reports grants and personal fees from Chugai Pharmaceutical, grants from Daiichi Sankyo, MSD, Pfizer Japan, outside the submitted work. M.S. reports grants and personal fees from Taiho Pharmaceutical Co., LTD, Chugai Pharmaceutical Co., LTD, MSD K.K, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K.K., personal fees from AstraZeneca Co., Ltd, outside the submitted work. T.Y. reports grants and personal fees from Takeda, Chugai, Taiho, Ono, Bayer, personal fees from Boehringer Ingelheim, Pfizer, Sysmex, Gilead Sciences, AstraZeneca, MSD, Sanofi, Otsuka, Kyowa Kirin, grants from Daiichi-Sankyo, Astellas, outside the submitted work. M.A. reports grants from Kyowa Kirin, Co. Ltd., outside the submitted work. K.K. reports grants and personal fees from Ono, Boehringer Ingelheim, personal fees from Chugai, MSD, AstraZeneca, Eli Lilly, Daiichi Sankyo, Bristol Myers Squibb, Kyowa Hakko KIRIN, Taiho, outside the submitted work. M.T. reports grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Covidien Japan, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, personal fees from Bristol-Myers Squibb, Johnson & Johnson, Nippon Kayaku, and grants from KM Biologics, outside the submitted work. TS reports grants and personal fees from Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, MSD, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical, grants from AbbVie, Kissei Pharmaceutical, LOXO Oncology, Merck Biopharma, personal fees from AstraZeneca, Bristol-Myers Squibb, Covidien Japan, Kyowa Hakko Kirin, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Taiho Pharmaceutical, Thermo Fisher Scientific, Precision Medicine Asia, outside the submitted work. N.Y. reports grants and personal fees from MSD K.K., Chugai Pharmaceutical CO., LTD., ONO PHARMACEUTICAL CO., LTD., DAIICHI SANKYO CO., LTD., TAIHO PHARMACEUTICAL CO., LTD., Takeda Pharmaceutical CO., LTD., Eli Lilly Japan K.K., Boehringer-Ingelheim, Novartis, Pfizer Inc., AstraZeneca, personal fees from Thermo Fisher Scientific, Bristol-Myers Squibb, Life Technologies Japan Ltd., NIPPON KAYAKU, Merk Biopharma, grants from Astellas Pharma Inc., TSUMURA & CO., SHIONOGI Co., Ltd., AbbVie GK., Amgen Inc., KYORIN Pharmaceutical Co., Ltd., Eisai Co., Ltd., TERUMO CORPORATION, Toppan Printing Co., Ltd., TOSOH, outside the submitted work. A.G. reports personal fees from Taiho, Nihon Kayaku, AstraZeneca, Chugai, Ono, Behringer-Ingelheim, outside the submitted work. All other authors declare no competing interests. Ethics Approval Statement: The study was approved by the Clinical Research Ethics Committee of each participating institution and written informed consent was obtained from each patient prior to participation in the study. It was conducted in accordance with the principles of the Declaration of Helsinki, 2013.