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