Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Jun:204:108584.
doi: 10.1016/j.lungcan.2025.108584. Epub 2025 May 16.

A treatment-related death predictive score for treatment-naïve advanced non-small cell lung cancer

Shogo Nomura  1 , Yuta Sekino  2 , Yoshimasa Shiraishi  3 , Yukihiro Toi  4 , Tatsuya Yoshida  5 , Kentaro Tanaka  3 , Shinichiro Suzuki  6 , Koichi Azuma  7 , Satoshi Hara  8 , Ryo Morita  9 , Seiji Niho  10 , Takuyuki Koda  11 , Ryo Toyozawa  12 , Kiyotaka Yoh  13 , Takayasu Kurata  14 , Haruhiko Fukuda  2 , Yuichiro Ohe  5 , Isamu Okamoto  3
Affiliations
Randomized Controlled Trial

A treatment-related death predictive score for treatment-naïve advanced non-small cell lung cancer

Shogo Nomura et al. Lung Cancer. 2025 Jun.

Abstract

Background: Combined chemotherapy with nivolumab and ipilimumab (NIC) improves survival outcomes in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC). However, these patients have a higher incidence of treatment-related deaths (TRDs), especially due to NIC. This study aimed to devise a risk stratification score for selecting patients with lower or higher TRD risk.

Methods: A dataset from the JCOG2007 study was used, which compared NIC with combined chemotherapy with pembrolizumab (PC). The TRD score was built from an adaptive LASSO regression analysis.

Results: The JCOG2007 study randomly assigned 295 patients to the PC (n = 147) and NIC (n = 148) arms, respectively. The TRD score was constructed for 124 patients who underwent NIC and had no missing covariates. The dichotomized TRD score was built and stratified all treated 290 (all enrolled 295) patients into 92 (92) high-risk and 198 (203) low-risk patients. No apparent differences in TRD incidence were observed in low-risk patients (2.2 % [0/92] with PC and 2.8 % [3/106] with NIC); however, this difference was noteworthy in high-risk patients (1.9 % [1/52] with PC and 20.0 % [8/40] with NIC). Of the 295 patients, the hazard ratios for death were 0.894 (0.553-1.444) in low-risk patients and that was 1.215 [0.696-2.122] in high-risk patients. Worse outcomes in the NIC arm were consistently observed for both immune-related adverse events (irAEs) and progression-free survival.

Conclusions: Although further validation studies with external data inside and outside Japan are required, the TRD score is a valuable tool for identifying patients with comparable toxicity-efficacy profiles among PC and NIC regimens.

Keywords: Immune-related adverse events; Immuno-checkpoint inhibitors; Non-small cell lung cancer; Treatment-related deaths.

PubMed Disclaimer

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: [Dr. Nomura reported receipt of personal fees and honoraria for lectures (AstraZeneca, Chugai Pharmaceutical, Kyowa Hakko, Byer, Asahi-Kasei Pharma, MSD, Takeda, and Eli Lilly); grants and research funding to the institution (AstraZeneca, MSD, Chugai); and consultancy (Asahi-Kasei Pharma, Daiichi Sankyo). Dr. Shiraishi reported receipt of personal fees and honoraria for lectures (Ono Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Taiho Pharmaceutical, Chugai Pharmaceutical, and Kyowa Kirin) and grants to the institution (Chugai Pharmaceutical). Dr. Toi reported receipt of personal fees and honoraria for lectures (Bristol-Myers Squibb, Ono Pharmaceutical, MSD K.K., AstraZeneca, Chugai Pharmaceutical, and Taiho Pharmaceutical). Dr. Yoshida reported receipt of personal fees and honoraria for lectures (Novartis, Daiichi-Sankyo, AstraZeneca, MSD, Chugai Pharmaceutical, BMS, Ono Pharmaceutical, Takeda, Pfizer, Lilly, and Merck Biopharma); grants and research funding to institution (Novartis, AbbVie, Amgen, Daiichi-Sankyo, AstraZeneca, MSD, Chugai Pharmaceutical, Astellas, Boehringer Ingelheim, BMS, Ono Pharmaceutical, and Merck Biopharma); and participation on advisory boards (Novartis, MSD, Amgen, Chugai Pharmaceutical, Daiichi-Sankyo, Pfizer, and Boehringer Ingelheim). Dr. Tanaka reported receipt of personal fees and honoraria for lectures (Ono Pharmaceutical, Bristol-Myers Squibb). Dr. Suzuki reported receipt of grants to the institution (Nippon Boehringer Ingelheim). Dr. Azuma reported receipt of personal fees and honoraria for lectures (AstraZeneca, MSD, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Takeda Pharmaceutical). Dr. Morita reported receipt of personal fees and honoraria for lectures (AstraZeneca, Chugai, Daiichi-Sankyo). Dr. Niho reported receipt of personal fees and honoraria for lectures (AstraZeneca, Chugai, Eli Lilly, Daiichi Sankyo, MSD, Ono, Takeda, Eisai, Pfizer, Kyorin, Taiho, Nippon Kayaku, Novartis, Amgen, Boehringer Ingelheim, Merck, Kyowa Kirin); grants to institution (Chugai, Eli Lilly, Taiho, Boehringer Ingelheim, Shionogi, Kyowa Kirin, Teijin, GlaxoSmithKline, Daiichi Sankyo, Ono, Kyorin); and consultancy (AstraZeneca, Daiichi Sankyo). Dr. Koda reported receipt of personal fees and honoraria for lectures (AstraZeneca). Dr. Toyozawa reported receipt of personal fees and honoraria for lectures (AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Thermo Fisher Scientific); grants to institution (AbbVie, Amgen, AnHeart Therapeutics, Daiichi Sankyo, Eli Lilly Japan, MSD, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical). Dr. Yoh reported receipt of personal fees and honoraria for lectures (Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Daiichi Sankyo, Kyowa Kirin, Lilly, MSD, Ono Pharmaceutical, Takeda); grants to institution (Abbvie, Amgen, ArriVent Biopharma, AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, Lilly, MSD, Taiho, Takeda); and consultancy (Boehringer Ingelheim, Abbvie). Dr. Kurata reported receipt of personal fees and honoraria for lectures (MSD, Ono, Bristol Myers, Eli Lilly, AstraZeneca, Chugai, Pfizer, Nippon Kayaku, Takeda); and grants to the institution (MSD, Ono, Amgen, AstraZeneca, Novartis, Chugai, Janssen, Takeda, Daiichi Sankyo). Dr. Fukuda reported receipt of grants and research funding to the institution (AstraZeneca, Ono Pharmaceutical, Chugai Pharmaceutical, Takeda Pharmaceutical) and consultancy (Chugai Pharmaceutical, Kyowa Kirin, CMIC). Dr. Ohe reported receipt of personal fees and honoraria for lectures (AstraZeneca, Chugai, Eli Lilly, Ono, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Kirin, Eisai, Daiichi-Sankyo); and grants to institutions (AstraZeneca, Chugai, Eli Lilly, Kirin, Sumitomo, Pfizer, Taiho, Novartis, Takeda, Daiichi-Sankyo, Janssen). Dr. Okamoto reported receipt of personal fees and honoraria for lectures (Daiichi Sankyo, Lilly, Chugai Pharma, Bristol-Myers Squibb, MSD Oncology, AstraZeneca, Taiho Pharmaceutical, Ono Pharmaceutical, Boehringer Ingelheim, GSK). No other disclosures were reported from Dr. Sekino and Dr. Hara].

Publication types

MeSH terms

LinkOut - more resources