Monotherapy with trabectedin did not demonstrate an improvement in survival when compared with standard chemotherapy for patients with BRCA-mutated and BRCAness phenotype ovarian cancer, according to data from a phase 3 trial presented at the 2022 ASCO Annual Meeting.

“Trabectedin demonstrated antitumor activity when administered as a single agent in relapsed platinum sensitive ovarian cancer, with an overall response rate (ORR) ranging from 26% to 43% and a median progression-free survival (PFS) of 5 months,” wrote Giovanni Scambia, MD, Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica, Rome, Italy, and colleagues.

“In addition, trabectedin showed 39.4% response rate, 4.5 months median PFS and 18 months median overall survival (OS) in a single arm phase 2 trial in recurrent BRCA mutated and/or the BRCAness phenotype ovarian cancer patients,” they continued.

Thus, Dr Scambia et al conducted an open-label, phase 3 study of 244 patients with recurrent ovarian cancer harboring BRCA 1/2 mutations or with BRCAness phenotype who were randomized to receive trabectedin 1.3 mg/mq every 21 days or physician’s choice of chemotherapy (eg, carboplatin, gemcitabine, weekly paclitaxel, pegylated liposomal doxorubicine, or topotecan).

The primary end point of the study was OS, and the secondary end points were PFS, ORR, and duration of response.

The investigators calculated the sample size based on the assumption that trabectedin would increase the median OS from 10 to 15 months (2-sided log-rank test at the error alfa = 0.05 and a power of 80%). Furthermore, they used the Kaplan-Meier method and log-rank test to compute and analyze medians and lifetables; a Cox proportional hazards model was used to evaluate treatment efficacy.

At the point of median follow (40 months), patients given trabectedin versus physician’s choice of chemotherapy had a median PFS of 4.4 months and 4.9 months, respectively (hazard ratio, 1.03; P = .848) and a median OS of 17.9 months and 15.8 months, respectively (hazard ratio, 1.15; P = .304).

The overall response rate was 20.2% with standard chemotherapy and 15.4% with trabectedin, and there were no superior effects observed with trabectedin in the pre-specified sub-group analysis based on BRCA mutational status, type of chemotherapy, and platinum-free interval.

Of note, Dr Scambia et al did not report any new signals of toxicity for the chemotherapies used.

“Trabectedin as a single agent does not improve survival outcomes when compared to standard chemotherapy in BRCA mutation and BRCAness phenotype ovarian cancer patients,” they concluded.

Source:

Scambia G, Raspagliesi F, Valabrega G, et al. Randomized phase III trial on trabectedin (ET-743) single agent versus clinician’s choice chemotherapy in recurrent ovarian, primary peritoneal, or fallopian tube cancers of BRCA-mutated or BRCAness phenotype patients (MITO23). Presented at: the 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL, and virtual. Abstract LBA5504.