As reported in the Journal of Clinical Oncology by Domenica Lorusso, MD, PhD, and colleagues, the Italian phase III MITO-23 trial showed no overall survival benefit with trabectedin vs chemotherapy in women with recurrent ovarian cancer with a BRCA mutation or BRCAness phenotype.
Domenica Lorusso, MD, PhD
Study Details
In the open-label multicenter trial, 244 patients were randomly assigned between April 2016 and December 2018 to receive trabectedin at 1.3 mg/m2 every 3 weeks (n = 122) or physician’s choice of chemotherapy (n = 122) consisting of pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin. Overall, 34.8% of patients had a BRCA1 mutation; 14.3% had a BRCA2 mutation; and 50.8% had BRCAness phenotype, defined as response to two or more prior platinum-based treatments.
In total, 70.5% of patients had received at least three lines of chemotherapy and 35.7% had received a PARP inhibitor. The primary endpoint was overall survival in the intention-to-treat population.
Key Findings
Median overall survival was 15.8 months (95% confidence interval [CI] = 11.8–22.3 months) in the trabectedin group vs 17.9 months (95% CI = 15.2–23.6 months) in the chemotherapy group (hazard ratio [HR] = 1.15, 95% CI = 0.88–1.51, P = .304).
Median progression-free survival was 4.9 months vs 4.4 months (HR = 1.02, 95% CI = 0.79–1.31, P = .897). Prespecified exploratory analyses showed no superiority of trabectedin in terms of overall survival or progression-free survival according to BRCA mutational status, type of chemotherapy used in the chemotherapy group, number of previous chemotherapy lines, previous PARP inhibitor treatment, or platinum sensitivity.
Among 208 patients evaluable for response, objective response was observed in 17.1% of 105 patients in the trabectedin group vs 21.4% of 103 in the chemotherapy group; median response durations were 5.62 months vs 5.66 months.
Grade ≥ 3 adverse events occurred in 71.1% of patients in the trabectedin group, most commonly neutropenia (34.7%), fatigue (15.7%), and hepatic toxicity (14.9%), vs 50.0% of the chemotherapy group, most commonly neutropenia (12.7%), thrombocytopenia (8.5%), and fatigue (6.8%). Serious adverse events occurred in 24.8% vs 5.9% of patients. No treatment-related deaths were observed.
The investigators concluded, “Trabectedin did not improve median overall survival and showed a worse safety profile in comparison with physician’s choice control chemotherapy [in women with recurrent ovarian cancer with a BRCA mutation or BRCAness phenotype].”
Dr. Lorusso, of Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of Sacred Heart, Rome, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by PharmaMar, S.A. For full disclosures of the study authors, visit ascopubs.org.
