1243MO - A phase III study comparing weekly carboplatin plus nab-paclitaxel and daily low-dose carboplatin for concurrent chemoradiotherapy in elderly patients (≥75 years) with unresectable locally advanced NSCLC: JCOG1914

Background

Daily low-dose carboplatin (CBDCA) plus concurrent thoracic radiotherapy (cTRT), followed by durvalumab maintenance therapy, is the standard treatment for elderly patients (pts) with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) in Japan. While, a phase I study suggested that weekly CBDCA and nab-paclitaxel (nPTX) plus cTRT have comparable efficacy outcomes with more manageable adverse events.

Methods

To confirm whether weekly CBDCA+nPTX (arm B) is noninferior to daily CBDCA (arm A) for concurrent chemoradiotherapy, treatment-naïve LA-NSCLC pts (≥75 years) with a performance status of 0 or 1 were randomized in a 1:1 ratio. We planned to enroll 166 pts from 49 institutions in 3.5 years. The primary endpoint was overall survival (OS) with a noninferiority margin of 1.27 for the upper limit of the 95% CI of the hazard ratio (HR). The secondary endpoints included progression-free survival (PFS), adverse events, and proportion of pts without deterioration in the Functional Assessment of Cancer Therapy–Trial Outcome Index (FACT-TOI).

Results

The planned first interim analysis was performed on March 2024 for 100 pts (50 pts in each arm) enrolled between December 2020 and September 2023. The Data and Safety Monitoring Committee recommended an early termination due to futility. Patient backgrounds were as follows; median age was 79 years (range 75-89), stage was IIIA in 40%, IIIB in 48% and IIIC in 11%, histology was adenocarcinoma in 42% pts. With a median follow-up of 10.8 months (mo), the median OS was 30.8 mo in arm A vs. 26.1 mo in arm B (HR 1.766, 95% CI 0.800 to 3.901). A predicted probability of showing a non-inferiority of arm B at the final analysis was only 8.0%. The median PFS was 12.2 vs. 13.8 mo (HR 0.977; 95% CI 0.554 to 1.723). Treatment-related deaths occurred in two pts in arm B due to sepsis and pneumonitis. The proportion of pts without FACT-TOI deterioration at 6 weeks were 33/50 (66%) in arm A vs. 24/50 (48%) in arm B (odds ratio 0.483, 95% CI 0.215 to 1.085; p=0.078).

Conclusions

CBDCA+cTRT remains the standard treatment for elderly pts with unresectable LA-NSCLC in Japan.

Clinical trial identification

jRCTs031200230.

Editorial acknowledgement

Legal entity responsible for the study

Japan Clinical Oncology Group.

Funding

This research was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number JP23ck0106684h0003 and National Cancer Center Research and Development Funds (2023-J-03).

Disclosure

S. Omori: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Japan Eli Lilly Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Amgen K.K., AstraZeneca K.K., Kyowa Kirin Co., Ltd., MSD K.K., Bristol Myers Squibb K.K., Novartis Pharma K.K. H. Kenmotsu: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co, Ltd., Ono Pharmaceutical Co, Ltd., Boehringer Ingelheim, Eli Lilly K.K, Kyowa Hakko Kirin Co., Ltd., Bristol Myers Squibb, MSD, Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., AstraZeneca K.K., Pfizer, Taiho Pharma, Merck, Amgen inc., Bayer, Takeda Pharmaceutical Co., Ltd, Guardant health Japan; Financial Interests, Institutional, Research Grant: AstraZeneca, Chugai Pharmaceutical Co, Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co, Ltd., LOXO Oncology, Eli Lilly K.K; Non-Financial Interests, Principal Investigator: AstraZeneca K.K., Eli Lilly K.K, Boehringer Ingelheim, Takeda Pharmaceutical Co., Ltd. T. Takahashi: Financial Interests, Institutional, Research Funding: AstraZeneca K.K., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Amgen inc., Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., AnHeart Therapeutics Inc. ; Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Chugai PHARMACEUTICAL Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., BMS Japan, Amgen K.K., Novartis Pharma K.K. S. Nomura: Financial Interests, Personal, Research Funding: AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K.; Financial Interests, Personal, Advisory Role: Asahi-Kasei Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Byer Japan, Asahi-Kasei Pharmaceutical Co., Ltd., MSD K.K., JMDC. H. Harada: Financial Interests, Personal, Invited Speaker: AstraZeneca, Brainlab; Financial Interests, Personal, Research Funding, Support for attending meetings and/or travel: Brainlab; Non-Financial Interests, Personal, Leadership Role, Japanese Radiation Oncology Study Group: West Japan Oncology Group. S. Ishikura: Financial Interests, Personal, Invited Speaker: Accuray Japan K.K., AstraZeneca K.K. H. Izumi: Financial Interests, Institutional, Research Funding: Amgen K.K., AbbVie Inc., Arrivent Biopharma, AstraZeneca K.K., Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Japan Eli Lilly Co., Ltd., Takeda Pharmaceutical Co., Ltd., Merck, Chugai Pharmaceutical Co., Ltd., MSD K.K. Y. Shinno: Financial Interests, Institutional, Research Funding: Ono Pharmaceutical Co., Ltd., Janssen Pharmaceutical, Japan Clinical Research Operations, Taiho Pharmaceutical Co., Ltd., Bayer, Gilead; Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical. M. Oki: Financial Interests, Institutional, Research Funding: AbbVie Inc, Chugai Pharmaceutical Co., Ltd., GSK K.K., MSD K.K., Parexel International Corporation., Sanofi K.K., AstraZeneca K.K., Fujifilm Toyama Chemical Co., Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Kaneka Medix Corp., Gilead Sciences, Inc., Daiichi Sankyo Co., Ltd.; Financial Interests, Personal, Invited Speaker: AMCO Inc., Canon Medical Systems Corp., Fujifilm Corp., Merit Medical Japan K.K., Olympus Marketing, Inc, AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Kaneka Medix Corp., Novartis Pharma K.K., Sanofi K.K., Eli Lilly Japan K.K., MSD K.K., Intuitive Surgical G.K., GSK K.K., Nippon Boehringer Ingelheim Co., Ltd., Merck Biopharma Co., Ltd. T. Masuda: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo pharmaceutical, Taiho pharmaceutical Payment for me, Boehringer Ingelheim, Eli Lilly, Ono pharmaceutical, Chugai pharmaceutical, AstraZeneca K.K., Otsuka, Kyowa Kirin. T. Yokoyama: Financial Interests, Institutional, Research Funding: AbbVie GK, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Delta-Fly Pharma, Janssen, MSD, Parexel International, Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Merck Biopharma, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Takeda. Y. Hosomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Kyowa Kirin, Nippon Kayaku, Takeda, Eisai, Novartis, Pfizer, MSD. T. Shimokawa: Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb, MSD. S. Murakami: Financial Interests, Institutional, Research Funding: AstraZeneca, Takeda Pharmaceutical, Chugai Pharmaceutical, Sanofi, MSD, Daiichi Sankyo, Ono Pharmaceutical, Janssen Pharmaceutical; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, MSD, Pfizer, Novartis, Taiho Pharmaceutical. H. Yoshioka: Financial Interests, Personal, Invited Speaker, Lecture fee: Eli Lilly Japan K.K., Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, MSD, AstraZeneca, Ono Pharmaceutical, Novartis Pharma, Kyowa Kirin, Otsuka Pharmaceutical, Amgen, Pfizer, Daiichi Sankyo, Nipro Pharma, Merck Biopharma; Financial Interests, Personal, Other, Consulting fee: Delta-Fly Pharma, Inc.; Financial Interests, Institutional, Local PI: Daiichi Sankyo, AstraZeneca, Jannsen Pharmaceutical, MSD, Novartis Pharma; Financial Interests, Institutional, Coordinating PI: Delta-Fly Pharma, Boehringer Ingelheim. H. Fukuda: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., CMIC Co., Ltd.; Financial Interests, Personal, Writing Engagement: m3.com. Y. Ohe: Financial Interests, Personal, Advisory Board: Amgen, AnHeart Therapeutics Inc, AstraZaneca, BMS, Celltrion, Nippon Kayaku, ONO, Pfizer, Takeda, PharmaMar, AnHeart; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, MSD, Novartis, ONO, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, Janssen, Amgen; Financial Interests, Personal and Institutional, Coordinating PI: Takeda, ONO; Non-Financial Interests, Leadership Role: JSMO, JLCS, JCOG; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.