Objective Chemotherapy for high-grade serous ovarian cancers in platinum-sensitive relapse includes carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin. According to in vitro data, BRCA mutated patients are sensitive to replicative stress agents but BRCA status is not yet used for the choice of chemotherapy at relapse. Our aim was to assess these doublets according to BRCA status in first platinum-sensitive relapse.
Methods The ESME ovarian cancer database comprises a multicenter retrospective cohort of patients with ovarian cancer treated in French cancer centers between January 2011 and December 2017. Patients with high-grade serous ovarian cancers at first platinum-sensitive relapse who received one of these doublets were included. The objective was to compare progression-free survival of each chemotherapy doublet according to BRCA status.
Results Among the 10 263 patients in the database, 1539 patients had a first platinum-sensitive relapse: 825 BRCA wild type patients (53.6%) and 304 BRCA mutated patients (19.8%) (7 patients had a homologous recombination mutation and BRCA status was unkown for 403 patients). Median progression-free survival was longer in BRCA mutated patients than in BRCA wild type patients when receiving carboplatin/pegylated liposomal doxorubicin without maintenance treatment (15.8 vs 11.8 months; p<0.001). In contrast, we observed no difference in patients treated with carboplatin/paclitaxel (14.6 vs 14.3 months, respectively; p=0.70) or in those treated with carboplatin/gemcitabine (12.0 vs 9.8 months, respectively; p=0.18). In BRCA wild type patients without maintenance, better progression-free survival occurred with carboplatin/paclitaxel (median progression-free survival 14.3 months) than with carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin (9.8 and 11.8 months, respectively; p=0.017). In BRCA mutated patients without maintenance, there was no difference between the three doublets (median progression-free survival of 14.6, 12.0, and 15.8 months with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin, respectively; p=0.40).
Conclusion While treatment with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin shows comparable efficacy in BRCA mutated patients, treatment with carboplatin/paclitaxel appears to be more effective than carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin in BRCA wild type patients with high-grade serous ovarian cancers at first platinum-sensitive relapse.
- Ovarian Cancer
- Neoplasm Recurrence, Local
- Cystadenocarcinoma, Serous
- BRCA1 Protein
Data availability statement
Data may be obtained from a third party and are not publicly available.
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Contributors MR conceptualized the study and is the guarantor of this work. FB-S, CS-M, MC and MR developed its methodology, conducted research investigation and performed data presentation. LB and MR supervised the study. FB-S and MR wrote and edited the first manuscript. All authors reviewed and approved the final manuscript.
Funding This work was supported by Unicancer. The ESME ovarian cancer database is supported by an industrial consortium (AstraZeneca and GlaxoSmithKline). Unicancer manages the ESME ovarian cancer database independently. MR was supported by the Interface INSERM program.
Competing interests MR received honoraria from AstraZeneca, MSD, GSK, Immunocore and grant support from Bristol-Myers Squibb and Merck. RS received honoraria from GSK, EISAI, and Novartis and declares research grants from AstraZeneca. TD declares advisory boards from Pfizer, AstraZeneca, GSK, Clovis Oncology, Roche, MSD, Mylan, and Tesaro, research grants from Novartis, Pfizer, MSD, abd Seagen and local PI from Roche, AstraZeneca, GSK, MSD, Pfizer, Netris Pharma, and Seagen. The other authors have no conflicts of interest to declare.
Provenance and peer review Not commissioned; externally peer reviewed.
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