(P 171) SEX DIFFERENCES IN OUTCOMES AND TOXICITY IN PATIENTS TREATED FOR SARCOMA IN A REFERENCE CENTER

Objective: In the era of precision medicine, despite mounting evidence that women might be more susceptible to toxicity from chemotherapy (CT), sex influence on treatment effects and the biology of non-sex-related cancers have largely been ignored. Due to their rarity, data on patients (pts) with sarcoma are scarce.

Methods: We reviewed data of pts with sarcoma treated with (neo)adjuvant and/or first line CT between 2015 and 2022 at Veneto Institute of Oncology. Delays/reductions were evaluated in the first 9 weeks of CT and expressed as relative dose intensity (RDI): ratio of delivered dose intensity (mg/m2 per week) to theorical dose intensity. Survival was analyzed by Kaplan-Meier, and comparisons among groups studied through log-rank and Cox regressions. Sex differences in RDI, adverse events (AEs) and impact of RDI on disease-free survival (DFS), progression-free survival (PFS) and overall survival (OS) were analyzed.

Results: Overall, data for 197 pts were available (109 treatments for localized disease: 69 neoadjuvant/40 adjuvant setting; 127 first line treatments for advanced disease). Median age was 57 years (IQR: 41-67; range: 17-83), males were 112 (57%). Soft tissue sarcomas were 167 (85%), bone sarcomas were 30 (15%). Most frequent histological subtypes were leyomiosarcoma, liposarcoma, angiosarcoma, Ewing-sarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma. Grade ≥ 3 AEs were observed in 60% of pts. Male had a lower risk of severe non-hematologic AEs (OR 0.5; p=0.04), while no significant sex differences were observed for all severe AEs. Dose was reduced upfront in 46% of female Vs 28% of males (p=0.007) . Also, males less often had RDI < 85% (OR 2.4; p=0.002). Survival outcomes were similar in both sexes, though comparisons might suffer from biases due to different distribution of histotypes within sexes. In the localized disease setting, worse survival was observed for males receiving RDI < 85% compared to ≥85% (median OS 36.6 months, 95% CI 23.7-NA Vs 63.7 months, 95% CI 51.1-NA, p=0.004; median DFS 11.1 months, 95% CI 5.3-NA Vs 26.3 months, 95% CI 15.9-NA, p=0.03) whereas no significant differences at the 85% threshold of RDI were found for females.

Conclusion: Greater risk of AEs and lower RDI in women treated for sarcoma add to the evidence that a sex-difference in treatment delivery and outcomes exists. Despite a global lower RDI, survival outcomes for female were not worse compared to male. Interestingly, RDI < 85% did not negatively affect survival outcomes in women (standard dosing based on “male” standards?). Such data call for optimization of drug dosing by sex to be considered in trial design.