Randomized Prospective Comparison Between Neoadjuvant Mitomycin C Plus Cisplatin and Paclitaxel Plus Carboplatin in Patients With BRCA1-Associated Ovarian Cancer.

Neoadjuvant mitomycin C plus cisplatin (MP) previously demonstrated promising activity in high-grade serous ovarian cancer in a single-arm study of BRCA1 pathogenic variant (PV) carriers. This prospective, open-label, randomized Phase II trial (NCT04747717) compared MP with standard paclitaxel-carboplatin (TCbP) in women with germline BRCA1/2 PVs. Here, we report a per-protocol analysis of the BRCA1 subgroup involving 29 MP and 31 TCbP patients. Grade III-IV anemia and thrombocytopenia were more frequent with MP, while other adverse events showed similar distribution. RECIST v1.1 response rates did not differ between treatment arms. Surgery was undertaken for 25 MP and 28 TCbP patients. Complete cytoreduction was achieved in 20/25 (80%) MP and 19/28 (68%) TCbP cases. All MP patients underwent complete debulking after 3-4 neoadjuvant cycles, while six out of 19 women from the TCbP arm required more than 4 cycles to achieve surgical clearance of tumor lumps (p = 0.008). MP outperformed TCbP in the improvement of the peritoneal cancer index (p = 0.001). Complete absence of tumor cells in the omentum was documented in 4/25 (16%) MP patients and 6/28 (21%) TCbP patients (p = 0.73). Maintenance olaparib, complete cytoreduction, resolution of carcinomatosis, and TP53 mutation type (loss-of-function (LOF) versus non-LOF) were associated with improved disease-free interval (DFI). At a median follow-up of 44.8 months, multivariate analysis revealed no differences in progression-free survival or DFI between treatment arms. In conclusion, MP showed no significant efficacy advantage over TCbP but produced a rapid and profound reduction of tumor burden, thus warranting further evaluation. Trial Registration: ClinicalTrials.gov (identifier: NCT04747717).