Therapeutic Advances in Medical Oncology

Factors associated with accepting chemotherapy despite the risk of fertility loss in Latin American breast cancer patients—LACOG 0414 study

Background: Fertility loss due to chemotherapy is a major concern for young patients with breast cancer (BC), influencing treatment decisions and quality of life. Despite established guidelines recommending fertility counseling, access to fertility preservation remains limited in Latin America. Objectives: This study evaluated attitudes and preferences regarding fertility-related concerns and chemotherapy decision-making among young Latin American women with early-stage BC. Design: A prospective cohort study was conducted at seven institutions in Brazil, Mexico, and Peru. Methods: Premenopausal women aged 18–40 years with stage I–III BC requiring (neo)adjuvant chemotherapy completed a fertility questionnaire before treatment, along with validated quality-of-life assessments (EORTC QLQ-C30 and EORTC QLQ-BR23). One year after chemotherapy initiation, the patients were reassessed for ovarian function status and quality of life. Factors associated with chemotherapy acceptance despite potential infertility risks were analyzed using univariate and multivariate Poisson regression models. Results: A total of 270 patients were included (mean age, 33.9 years). Prior to diagnosis, 41.5% of the women had children, and 31.1% expressed a desire for future childbearing. Among the participants, 8.5% were unaware of chemotherapy-induced infertility risks, 21.5% would decline chemotherapy if the infertility risk exceeded 25%, and 20.0% would accept treatment despite a 76%–100% infertility risk. In addition, 44.1% of patients required at least a 20% increase in survival probability to accept chemotherapy. In the multivariate analysis, married patients were significantly less likely to refuse chemotherapy (risk ratio: 0.88, 95% confidence interval: 0.82–0.94; p  < 0.01). One year post-treatment, 73.1% of the patients experienced chemotherapy-induced amenorrhea. Conclusion: Fertility concerns significantly impact chemotherapy decision-making in young Latin American patients with BC. Limited fertility awareness, socioeconomic disparities, and restricted access to fertility preservation contribute to these challenges. Strengthening fertility counseling and improving access to preservation options are essential for supporting informed treatment decisions in this population. Trial registration ( ClinicalTrials.gov ): NCT02862990.

SALVOVAR: a pragmatic randomized phase III trial comparing the SALVage weekly dose-dense regimen to the standard 3-weekly regimen in patients with poor prognostic OVARian cancers

Background: Patients with epithelial ovarian cancer (EOC) receiving neoadjuvant platinum-based chemotherapy (NACT) who remain ineligible for complete interval cytoreductive surgery (ICS) due to poor chemosensitivity (CA-125 KELIM™ score <1.0) have a poor prognosis (~20% 5-year survival). A weekly dose-dense carboplatin–paclitaxel regimen may improve outcomes in this high-risk subgroup. Objectives: To demonstrate the superiority of a salvage weekly dose-dense carboplatin–paclitaxel regimen over continuation of the standard 3-weekly regimen in poor-prognosis EOC patients after 3–4 cycles of standard NACT. Design: SALVOVAR is a pragmatic, open-label, multicenter, international, randomized phase III trial. Methods and analysis: Patients with stages III–IV high-grade EOC are eligible if they present (1) an unfavorable standardized KELIM score <1.0, and (2) a disease not amenable to complete ICS after 3–4 cycles of standard 3-weekly carboplatin–paclitaxel. Patients are randomized (1:1) to either the experimental arm (dose-dense carboplatin AUC5 day 1 plus paclitaxel 80 mg/m 2 on days 1, 8, and 15, every 3 weeks) or the control arm (continuation of the standard regimen) for 3 cycles. Bevacizumab use is allowed at investigator discretion. Stratification factors include planned bevacizumab administration, BRCA mutation status, and KELIM strata. The two co-primary endpoints are (1) improvement in late complete cytoreduction rates (from 5% in the control arm to 20% in the experimental arm), and (2) overall survival (target hazard-ratio, 0.61). Total 250 patients will be randomized. Secondary endpoints include objective response rate, progression-free survival, and safety. Additional planned analyses include quality-of-life, cost-effectiveness, surgical standardization, human sciences, and biology studies. Ethics: The protocol was approved by the national ethics committee and health authorities. Discussion: SALVOVAR will evaluate whether chemotherapy densification improves outcomes in poorly chemosensitive advanced EOC. If positive, this pragmatic strategy could be implemented in large-scale studies, independent of resource setting. Trial registration: ClinicalTrials.gov NCT06476184 (June-2024). Available at: https://clinicaltrials.gov/study/NCT06476184