Résumé
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/m2 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
Plain language summary
SALVOVAR: a study evaluating whether intensifying chemotherapy improves outcomes in patients with advanced ovarian cancer who show an insufficient response to initial treatment
Introduction:
Some women with advanced ovarian cancer get chemotherapy before surgery. If the cancer doesn’t respond well and doctors can’t remove it completely, the outlook is poor: only about 1 in 5 women live for 5 years. The KELIM score, which measures how quickly the CA-125 blood marker drops during treatment, helps show how sensitive the cancer is to chemotherapy. A low score (<1.0) means the cancer isn’t responding well. New studies suggest that giving chemotherapy weekly instead of every three weeks may help improve results in these high-risk patients.
Aim:
The SALVOVAR trial is testing whether stronger chemotherapy can help women with advanced ovarian cancer that does not respond well to treatment and cannot be fully removed with surgery after standard chemotherapy.
Method:
This is a large international study (phase III) for women with advanced high-grade ovarian cancer (stage III and IV). To join, patients must have already received 3 to 4 rounds of standard chemotherapy before surgery, have a low KELIM score (<1.0), and have cancer that cannot be fully removed by surgery.
Participants are randomly assigned to one of two groups:
- Experimental group: weekly carboplatin and paclitaxel (dose-dense chemotherapy)
- Standard group: chemotherapy every 3 weeks
Doctors may also add bevacizumab if they think it is appropriate.
The main goals are to see how many women can later have complete surgery after chemotherapy and to measure overall survival. Other goals include tumor response, time until the cancer gets worse, treatment safety, and how patients feel during treatment.
Discussion:
SALVOVAR will test if giving chemotherapy more often (dose-dense) helps high-risk patients do better. If it works, this simple treatment could be used everywhere, even in places with fewer medical resources.