Sex differences in toxicities and survival outcomes among Japanese patients with Stage III colorectal cancer receiving adjuvant fluoropyrimidine monotherapy: A pooled analysis of 4 randomized controlled trials (JCOG2310A).

Background: Fluoropyrimidine remains the key agent of adjuvant chemotherapy for stage III colorectal cancer (CRC). Western studies have shown that female sex is a favorable prognostic factor after surgery, but it is also a risk factor for adverse events (AEs) during adjuvant chemotherapy with fluoropyrimidine. However, little is known about whether sex differences in treatment outcomes exist in this setting in the Asian population.
Methods: Patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy in 4 randomized controlled trials were analyzed. Incidences of AEs and survival outcomes were compared between female and male patients.
Results: A total of 3170 patients (female, 1516; male, 1654) were included in this analysis. Compared with males, females were less likely to have a relative dose intensity (≥90 %: female 59.1 % vs. male 67.6 %), with a higher proportion of requiring dose reduction (28.8 % vs. 20.4 %) and a lower proportion of completing adjuvant chemotherapy (77.0 % vs. 81.7 %). Multivariable analyses demonstrated that female sex was associated with a higher incidence of grade 3-4 AEs (odds ratio 1.80 [95 % CI 1.51-2.14]). Female sex was identified as a favorable prognostic factor for overall survival (hazard ratio [HR]: 0.80 [0.65-0.97]) and relapse-free survival (HR: 0.73 [0.63-0.85]) in multivariable analyses. Female patients had fewer time-to recurrence (TTR) events than male patients (5-year TTR: 17.7 % vs. 22.3 %).
Conclusion: Sex had implications for the development of AEs and survival outcomes of Japanese patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. The authors declare the following financial interests/personal relationships that are considered potentially competing interests. H.H. has received honoraria from Bristol-Myers Squibb Japan, Chugai Pharma, Fujifilm, Novartis, Taiho Pharmaceutical, and Teijin Pharma, and has received research funding from BeiGene. A.D.W. has received payment for expert testimony from Astellas, has received support for attending meetings and/or travel from Servier, and Merck KG, has received consulting or advisory fees from MSD, Astra-Zeneca, Astellas, BMS, Pierre Fabre, and Dragonfly, and has other financial or non-financial interests. T.H. has received grands or contracts from Taiho Pharm, Chugai Pharma, Ono Pharmaceutical, BeiGene, Astellas Pharma, AstraZeneca, Pfizer, Bristol Myer Squibb, and Incyte Japan, and had received honoraria from Chugai Pharma, Merck Serono, Takeda, Taiho Pharmaceutical, Ono Pharmaceutical, Yakult Pharmaceutical, Lilly, Bristol-Myers Squibb Japan, Bayer, Daiichi-Sankyo, and Astellas. J.M. has received honoraria from Chugai pharmaceutical, Taiho pharmaceutical, his spouse is an employee of Pfizer. A.T. has received grands or contracts from Merck Sharp & Dohme, AstraZeneca, Amgen, Eisai, Bristol-Myers Squibb, and Ono Pharmaceutical, had received honoraria from Lilly, Ono Pharmaceutical, Taiho Pharmaceutical, Chugai Pharma, Takeda, and Merck Serono. All remaining authors have declared no conflicts of interest.
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