Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial

Authors

Domenica Lorusso

¹Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy

Domenica Lorusso, Francesco Raspagliesi, Dominique Ronzulli, Giorgio Valabrega, Nicoletta Colombo, Carmela Pisano, Chiara Cassani, Germana Tognon, Stefano Tamberi, Giorgia Mangili, Serafina Mammoliti, Ugo De Giorgi, Filippo Greco, Anna Maria Mosconi, Enrico Breda, Grazia Artioli, Claudia Andreetta, Claudia Casanova, Rita Ceccherini, Antonio Frassoldati, Vanda Salutari, Serena Giolitto, Giovanni Scambia

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PURPOSE

Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting BRCA mutation and/or BRCAness phenotype.

A prospective, open-label, randomized phase III MITO-23 trial evaluated the activity and safety of trabectedin 1.3 mg/m² given once every 3 weeks (arm A) in BRCA 1/2 mutation carriers or patients with BRCAness phenotype (ie, patients who responded to ≥two previous platinum-based treatments) with recurrent OC, primary peritoneal carcinoma, or fallopian tube cancer in comparison with physician's choice chemotherapy in the control arm (arm B; pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin). The primary end point was overall survival (OS) evaluated in the intention-to-treat population.

Overall, 244 patients from 21 MITO centers were randomly assigned (arm A = 122/arm B = 122). More than 70% of patients received ≥three previous chemotherapy lines and 35.7% had received a poly (ADP-ribose) polymerase inhibitor (PARPi) before enrollment. Median OS was not significantly different between the arms: arm A: 15.8 versus arm B: 17.9 months (P = .304). Median progression-free survival was 4.9 months in arm A versus 4.4 months in arm B (P = .897). Among 208 patients evaluable for efficacy, the objective response rate was 17.1% in arm A and 21.4% in arm B, with comparable median duration of response (5.62 v 5.66 months, respectively). No superior effect was observed for trabectedin in the prespecified subgroup analyses according to BRCA mutational status, chemotherapy type, and pretreatment with a PARPi and/or platinum-free interval. Trabectedin showed a higher frequency of grade ≥3 adverse events (AEs), serious AEs, and serious adverse drug reactions compared with control chemotherapy.

Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.