Melphalan as a Promising Treatment for BRCA-Related Ovarian Carcinoma.

Melphalan, as a bifunctional alkylating agent has been shown to be selectively efficient in BRCA-deficient case reports of epithelial ovarian cancer (EOC). The clinical benefit of melphalan on unselected platinum-resistant EOC population and stratified by BRCA status has not been clearly elucidated. We aimed to determine the response to melphalan in patients with recurrent EOC after platinum-based therapy. This retrospective observational study included patients with recurrent EOC treated with melphalan between February 2007 to July 2020. Eligibility criteria included having a histological confirmation of EOC, previous treatment with carboplatin plus paclitaxel regimens, and disease recurrence during treatment with or within 6 months of the end of the platinum-based chemotherapy. A total of 75 platinum-resistant EOC patients were enrolled. Median age was 69 years (range 41-82). Median of previous therapies before melphalan was 4 (range 1-7). We observed a median follow-up of 32 months (range 1-62), progression-free survival (PFS) and overall survival (OS) of 3.6 months (range 2.9-4.7) and 9.5 months (range 8.0-14.1), respectively. In the whole population, 1 complete response, 6 partial responses and 37 stable diseases were registered with an overall clinical benefit rate of 58.7%. In BRCA1/2 mutant patients, we showed a significant longer PFS compared to BRCA1/2 wild type patients (6.2 Our study represents the largest cohort of heavily-pretreated EOC patients receiving melphalan treatment. Here, we report a considerable clinical activity of melphalan chemotherapy, more evident in a subset of BRCA1/2 mutated patients. Prospective studies to validate these findings are warranted.

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Copyright © 2021 Conteduca, Scarpi, Farolfi, Brighi, Rossi, Gurioli, Lolli, Schepisi, Bleve, Gianni, Virga, Altavilla, Burgio, Menna and De Giorgi.

Déclaration de conflit d'intérêts

VC has served as consultant/advisory board member for Janssen, Astellas, Merck, AstraZeneca, Bayer; has received speaker honoraria or travel support from Astellas, Janssen, Ipsen, Bayer and Sanofi. UDG reports research support from AstraZeneca, Roche, and Sanofi; and consultancy fees from Astellas, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Merck, Pfizer, and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.