Early tumor shrinkage and depth of response in patients with advanced gastric cancer: a retrospective analysis of a randomized phase III study of first-line S-1 plus oxaliplatin vs. S-1 plus cisplatin
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We investigated early tumor shrinkage (ETS) and depth of response (DpR) using data from the G-SOX study comparing S-1 plus oxaliplatin with S-1 plus cisplatin as the first-line treatment for advanced gastric cancer (AGC).
ETS was determined as % decrease in the sum of the longest diameters of the target lesions at the first evaluation of week 6 compared to baseline. DpR was the maximum % shrinkage during the study treatment. The impact of ETS (cutoff value 20%) and DpR (continuous value) on progression-free survival (PFS) and overall survival (OS) were assessed by the log-rank test and Cox regression analysis including prognostic factors obtained in the G-SOX study; ECOG performance status, baseline sum of tumor diameters, disease status (recurrent/unresectable), and histology (diffuse/intestinal).
Among 685 patients enrolled in the G-SOX study, 632 patients who had the first tumor evaluation were analyzed. Patients with ETS ≥ 20% had longer PFS (median 4.5 vs. 2.8 months, p < 0.0001) and OS (median 14.8 vs. 10.5 months, p < 0.0001) than those with ETS < 20%. Adjusted hazard ratios of ETS < 20 vs. ≥ 20% were 0.606 (95% confidence interval (CI) 0.506–0.725) for PFS and 0.589 (95% CI 0.492–0.704) for OS. DpR was also significantly associated with PFS and OS (both p < 0.0001). These results were similar between the SOX and CS groups.
In AGC patients receiving the first-line therapy, ETS and DpR might be predictors for PFS and OS.
KeywordsGastric cancer Early tumor shrinkage Depth of response Oxaliplatin Chemotherapy
This work was supported by Yakult Honsha. We would like to thank all of the patients, investigators, and support staff who participated in the G-SOX study. We are also grateful to Atsushi Sato, Kunihisa Miyakawa, Tohru Fukushima, Tsuyoshi Morimoto, and Shinjiro Sakaino for performing extramural review to assess the objective response and PFS. We sincerely acknowledge the contribution of the late Chikuma Hamada, the former statistical advisor of the G-SOX study.
Compliance with ethical standards
Conflict of interest
Tomohiro Nishina has received honoraria from Yakult Honsha and Taiho Pharmaceutical. Kazuhiro Nishikawa has received grants and personal fees from Yakult Honsha, personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly and EA Pharma. Masahiro Gotoh has received grants, personal fees and non-financial support from Taiho Pharmaceutical, non-financial support from Yakult Honsha, personal fees and non-financial support from Bristol-Myers Squibb, Chugai Pharmaceutical, Takeda Pharmaceutical, Kyowa Hakko Kirin, Novartis Pharmaceutical, Sumitomo Dainippon Pharma, Bayer and Ono Pharmaceutical. Hideaki Bando has received research funds from Astra-Zeneca and Chugai Pharmaceutical, honoraria from Taiho Pharmaceutical and Eli Lilly. Naotoshi Sugimoto has received honoraria from Yakult Honsha, Taiho Pharmaceutical, Eli Lilly, Merck Serono and Chugai Pharmaceutical. Kenji Amagai has received research funding from Taiho Pharmaceutical and MSD. Akihito Tsuji has received honoraria from Yakult Honsha and Taiho Pharmaceutical. Kensei Yamaguchi has received personal fees from Taiho Pharmaceutical, Bayer, Bristol-Myers Squibb, Merck Serono, Chugai Pharmaceutical and Takeda Pharmaceutical. Hisateru Yasui has received personal fees from Medicon. Hisateru Yasui has received honoraria from Yakult Honsha, Taiho Pharmaceutical, Chugai Pharmaceutical, and Medicon Inc. Shuichi Hironaka has received honoraria from Yakult Honsha, Taiho Pharmaceutical, and Novartis Pharmaceutical. Ken Shimada has received honoraria from Yakult Honsha, Taiho Pharmaceutical, Chugai Pharmaceutical and Kyowa Hakko Kirin. Terukazu Mitome and Hiroki Kageyama are employees of Yakult Honsha, which produced oxaliplatin used in the G-SOX study from which data were obtained for the present analysis. Ichinosuke Hyodo has received advisory fees and honoraria from Yakult Honsha, Taiho Pharmaceutical and Chugai Pharmaceutical. The other authors have declared no conflicts of interest.
Human rights statement and informed consent
All procedures followed were in accordance with the ethical standards of the responsible committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or a substitute for it was obtained from all patients for being included in the study.
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