Trabectedin Did Not Improve Survival or Safety Among Patients With Recurrent Ovarian Cancer and BRCA-Mutation/BRCAness Phenotype

According to results from the phase 3 MITO-23 study, trabectedin did not improve overall survival (OS) and showed a worse safety profile compared to standard-of-care chemotherapy among patients with previously treated platinum-resistant or platinum-sensitive recurrent ovarian cancer with BRCA-mutated or BRCAness phenotype. 

Results from “several retrospective and prospective studies with trabectedin reported an improved response and a superior disease control rate in patients with BRCA germline mutation carriers compared with noncarriers,” stated Domenica Lorusso, MD, PhD, Catholic University of Rome, Italy, and coauthors.

This prospective, open-label study, enrolled 244 patients with platinum-resistant or platinum-sensitive recurrent ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer with BRCA 1⁄2 mutations or BRCAness phenotype who have either responded to at least 2 previous lines of platinum-based chemotherapy or were platinum-sensitive, who were not able or willing to receive further platinum-based treatments. Patients were randomized on a 1-to-1 basis to receive either 1.3 mg/m² of trabectedin once every 3 weeks (n = 122) or physician’s choice chemotherapy (n = 122). The primary end point was OS in the intention-to-treat population. Secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety. 

At analysis, median OS was 15.8 months in the trabectedin arm and 17.9 months in the control arm (P = .304). Median PFS was 4.9 months in the trabectedin arm and 4.4 months in the control arm (P = .897). ORR was 18% in the trabectedin arm and 22% in the control arm and DOR was 5.62 months and 5.66 months, respectively. No new or unexpected adverse events occurred and there were no treatment-related deaths. The most common grade ≥3 adverse events, the most common being neutropenia (34.7%), fatigue (15.7%), and hepatic toxicity (14.9%). In the control arm, 50% of patients experienced a grade ≥3 adverse events, the most common being neutropenia (12.7%), thrombocytopenia (8.5%), and fatigue (6.8%).

“Trabectedin has been tested in numerous trials in different settings for patients with [ovarian cancer], the majority of them negative,” stated JSCO Associate Editor Gini Fleming, MD, University of Chicago Medicine, Chicago, Illinois. “This trial does not support its use as a single agent specifically in subjects with either a BRCA1 or 2 mutation or who had responded to at least two prior platinum-based chemotherapy lines.” 

Dr Lorusso and coauthors concluded, “Ongoing translational analyses will possibly help in identifying predictive biomarkers of response/resistance to trabectedin and the patients who may gain long-term benefit from the treatment.”

Source: 

Lorusso D, Raspagliesi F, Ronzulli D, et al. 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. J Clin Oncol. Published online: February 5, 2024. doi:10.1200/JCO.23.01225