Trabectedin fails to improve survival outcomes in recurrent ovarian, primary peritoneal, or fallopian tube cancer

Trabectedin did not improve overall survival (OS) or progression-free survival (PFS) compared with chemotherapy in women with recurrent ovarian, primary peritoneal, or fallopian tube cancer and BRCA mutation or BRCAness phenotypes, according to results of the phase III MITO23 trial.

“The [MITO23] trial did not meet its endpoints of improving clinical outcome with respect to standard chemotherapy,” said study author Associate Professor Domenica Lorusso from the Fondazione Policlinico Gemelli IRCCS and Catholic University of Rome, Rome, Italy, who presented the findings at the ESMO Gynaecological Cancers Conference 2022.

The population comprised 244 patients (median age 60 years) with recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer with gBRCAm or BRCAness phenotype. Those with BRCAness (51 percent) had response to ≥2 prior platinum-based chemotherapy regimens. The patients were randomized 1:1 to receive either investigator’s choice of chemotherapy* (control) or intravenous trabectedin (1.3 mg/m² on day 1 Q3W).

Seventy-five percent of the population were diagnosed at stage III and 83 percent had high grade serous and endometrioid histology. Fifty-seven percent had a platinum chemotherapy-free interval of >6 months. Ninety-three percent had measurable disease at baseline. Seventy-one percent had ≥3 prior lines of treatment, with 35 percent having previous exposure to PARP inhibitors. The most common treatment regimens in the control arm were carboplatin, weekly paclitaxel, and pegylated liposomal doxorubicin (35.3, 20.5, and 16.4 percent, respectively).

After a median follow-up of 18.8 months, OS did not significantly differ between patients assigned to trabectedin or chemotherapy (median 15.8 vs 17.9 months; hazard ratio [HR], 1.15, 95 percent confidence interval [CI], 0.88–1.51; p=0.304). [ESMO Gynaecological Cancers Conference 2022, session: Clinical Trial Highlights]

PFS was also comparable between patients assigned to trabectedin and chemotherapy (median 4.9 vs 4.4 months; HR, 1.02, 95 percent CI, 0.79–1.31; p=0.897).

Overall response rate was 17.1 and 21.4 percent in the trabectedin and chemotherapy groups, respectively (p=0.142), with clinical benefit rates of 60.0 and 50.5 percent, respectively. Six and four patients, respectively, had complete response, 12 and 18 patients, respectively, partial response, and 45 and 30, respectively, stable disease. Duration of response was comparable between groups (median 5.62 vs 5.66 months; HR, 1.02, 95 percent CI, 0.54–1.94; p=0.955).

Grade ≥3 adverse events (AEs) occurred in 71.1 and 50.0 percent of trabectedin and chemotherapy recipients, respectively, and 24.8 and 5.1 percent, respectively, experienced serious AEs. Fifteen trabectedin recipients experienced serious adverse drug reactions compared with two chemotherapy recipients. AE-related dose reductions were comparable between groups (16.5 percent vs 16.1 percent), though more trabectedin than chemotherapy recipients discontinued treatment due to AEs (n=19 vs 7). There were no AE-related deaths in either group.

The most common grade ≥3 AEs with trabectedin vs chemotherapy were neutropenia (34.7 percent vs 12.7 percent), fatigue (15.7 percent vs 6.8 percent), and hepatic toxicity (14.9 percent vs 0.8 percent).

“[There were] no new safety issues raised from this study with respect to previously reported trabectedin safety profile,” remarked Lorusso.

According to Lorusso, treatment of recurrent epithelial ovarian cancer (rEOC) remains an unmet clinical need, which has a median OS of 2.5–3 years and 11–13 months in patients who are platinum sensitive and resistant, respectively, and median PFS of 8–13 and 3–5 months, respectively.

A prior phase II trial suggested that trabectedin could be an alternative regimen in patients who were unable to receive platinum chemotherapy. [Ann Oncol 2016;27:487-493]

“In this heavily chemotherapy and PARP pre-treated rEOC population, trabectedin reported retained clinical activity. [O]ngoing translational studies will possibly help in identifying predictive biomarkers of response or resistance to treatment,” she concluded.