Efficacy of chemotherapy according toBRCAstatus in patients with high-grade serous ovarian carcinoma at first platinum-sensitive relapse

ObjectiveChemotherapy for high-grade serous ovarian cancers in platinum-sensitive relapse includes carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin. According toin vitrodata,BRCAmutated patients are sensitive to replicative stress agents butBRCAstatus is not yet used for the choice of chemotherapy at relapse. Our aim was to assess these doublets according toBRCAstatus in first platinum-sensitive relapse.MethodsThe 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 toBRCAstatus.ResultsAmong the 10 263 patients in the database, 1539 patients had a first platinum-sensitive relapse: 825BRCAwild type patients (53.6%) and 304BRCAmutated patients (19.8%) (7 patients had a homologous recombination mutation andBRCAstatus was unkown for 403 patients). Median progression-free survival was longer inBRCAmutated patients than inBRCAwild type patients when receiving carboplatin/pegylated liposomal doxorubicin without maintenance treatment (15.8 vs 11.8 months; pBRCAwild 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). InBRCAmutated 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).ConclusionWhile treatment with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin shows comparable efficacy inBRCAmutated patients, treatment with carboplatin/paclitaxel appears to be more effective than carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin inBRCAwild type patients with high-grade serous ovarian cancers at first platinum-sensitive relapse.