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

116 Background: Fluoropyrimidine agents are the key component of adjuvant chemotherapy for pathological stage III colorectal cancer (CRC). Western studies have shown that female sex is associated with favorable survival outcomes after surgery, yet a risk factor for fluoropyrimidine-related adverse events (AEs) during adjuvant chemotherapy. However, it remains unclear whether there are sex differences in the treatment outcomes in this setting among the Japanese population. Methods: Patients enrolled in four randomized controlled trials (JCOG0205, JCOG0404, JCOG0910, and JCOG1006) who received adjuvant fluoropyrimidine monotherapy for pathological stage III CRC were analyzed. Incidences of AEs and survival outcomes (relapse-free survival [RFS], and overall survival [OS]) were compared between males and females. Multivariable logistic regression analyses were performed to evaluate associations between sex and the development of AEs. Multivariable Cox regression analyses were performed using Cox proportional hazard models to evaluate associations between sex and survival outcomes. Results: A total of 3170 patients (male, n = 1654; female, n = 1516) were included in the analysis. Compared with male patients, female patients were more likely to require dose reduction (male, 20.4%; female: 28.8%, p < 0.0001) and had low completion proportions of adjuvant chemotherapy (male, 81.7%; female, 77.0%, p = 0.0011). Female patients experienced higher incidences of any-grade hematological and non-hematological AEs (Table). Female sex was associated with higher incidences of grade 3/4 hematological AEs (odds ratio [OR]: 1.702 [95% CI 1.272–2.278], p = 0.0003) and non-hematological AEs (OR: 1.666 [95% CI 1.373–2.020], p < 0.0001). Female sex was identified as a favorable prognostic factor for RFS (hazard ratio [HR]: 0.729 [0.627–0.848], p < 0.0001) and OS (HR: 0.796 [0.653–0.970], p = 0.0238). Conclusions: Sex differences had implications for the development of AEs and survival outcomes of Japanese patients with pathological stage III CRC who received adjuvant fluoropyrimidine monotherapy. Incidences of adverse events. Adverse event Any grade Grade 3/4 Male% (95% CI) Female% (95% CI) p-value Male% (95% CI) Female% (95% CI) p-value Any hematological toxicity 63.7 (61.3–66.0) 83.9 (82.0–85.8) <0.0001 5.0 (4.0–6.1) 8.9 (7.5–10.4) <0.0001 Any non-hematological toxicity 93.3 (92.0–94.5) 96.1 (95.0–97.0) 0.0006 13.3 (11.7–15.1) 20.8 (18.8–22.9) <0.0001