Sex differences in toxicities among patients receiving regorafenib or trifluridine/tipiracil for refractory metastatic colorectal cancer: A subgroup analysis from the multicenter retrospective ReTrITA study.

e15589 Background: A mounting body of evidence indicates the existence of sex disparities in the prevalence, severity, and prognosis of various cancers. In the context of metastatic colorectal cancer (mCRC), women are observed to exhibit a higher propensity for right-sided tumour development, a heightened frequency of microsatellite instability, and an increased prevalence of BRAF mutant tumours. These characteristics are commonly correlated with a poor prognosis when treated with conventional chemotherapeutic combination therapies. In this substudy, the impact of sex on the toxicity of treatment with regorafenib (R) or trifluridine/tipiracil (T) for refractory mCRC was investigated. Methods: A retrospective analysis of clinical data pertaining to patients treated with R and T between 2012 and 2023 was conducted at 17 Italian cancer centres. Results: A total of 1156 patients were retrospectively enrolled in the ReTrITA study. These patients had received sequential treatment with T and R (T/R, n = 261; R/T, n = 155) or T (n = 427) or R (n = 313) as monotherapy. The majority of patients were male (n = 674; 58.4% vs. n = 482; 41.6%). Within the safety set, an amount of 488 cases of grade (G) 3/4 toxicity were identified in patients treated with T (43,4% in women and 56,6% in men), compared to 343 G3/G4 toxicities observed in patients receiving R (47,6% in females vs. 52,4% observed in males), representing 58.7% and 41.3% of all toxicity events, respectively. Notably, male patients treated with T were observed to have a higher incidence of grade G3/G4 toxicities, with the most common being neutropenia (31.1%) and diarrhoea (2.2%), in comparison with women who reported 25.2% and 2%, respectively; it is noteworthy that both sexes presented with grade 3/4 anaemia (8.1%) (p = 0.6988). In R-treated patients, men showed a significant but slightly higher prevalence of the most common G3/G4 toxicities than women, such as fatigue (15.7% vs. 12.2%) and hand-foot syndrome (10.2% vs. 9.3%), while female patients had a higher incidence of hypertension than males (4.6% vs. 4.3%) (p = 0.0582). Finally, the occurrence of febrile neutropenia in only four males who received therapy with T, should not be underestimated. Conclusions: Our real-world analysis suggests that the prevalence of G3/G4 toxicities in response to R or T therapy is lower among female patients than male patients, with the exception of hypertension. In order to enhance comprehension of toxicities associated with sex in the future, the analysis of toxicity events could represent a valuable instrument to facilitate the collection of extensive datasets, thereby enabling a more in-depth comparison of male and female patients. Furthermore, using patient-reported outcomes may help us gain a better knowledge of the impact of anticancer treatment based on sex and gender.