Add-on vistusertib misses mark in platinum-resistant, refractory ovarian high-grade serous carcinoma

Adding vistusertib to weekly paclitaxel does not appear to help improve clinical outcomes in patients with platinum-resistant or refractory ovarian high-grade serous carcinoma (PR-HGSC), according to the results of a phase II study.

The study included 140 patients (median age 63 years, 17.9 percent with platinum-refractory disease, 53.6 percent with ≥3 prior therapies) with PR-HGSC of ovarian, fallopian tube, or primary peritoneal origin and with measurable or evaluable disease (Response Evaluation Criteria in Solid Tumors version 1.1 and/or Gynecological Cancer Intergroup cancer antigen 125 criteria).

The patients were randomly assigned to receive weekly paclitaxel (80 mg/m² on days 1, 8, and 15 of a 28-day cycle) plus either oral vistusertib (50 mg twice daily) or placebo. The primary endpoint was progression-free survival in the intention-to-treat population. Secondary endpoints included response rate, overall survival, and quality of life.

Progression-free survival did not significantly differ between the vistusertib and placebo groups, with a median of 4.5 and 4.1 months, respectively (hazard ratio [HR], 0.84, 80 percent confidence interval [CI], 0.67–1.07; 1-sided p=0.18).

Likewise, there were no significant between-group differences observed in overall survival (median, 9.7 vs 11.1 months; HR, 1.21, 80 percent CI, 0.91–1.60) and response rate (odds ratio, 0.86, 80 percent CI, 0.55–1.36).

In terms of safety, grade 3 to 4 adverse events occurred in 41.2 percent of patients who received paclitaxel plus vistusertib and in 36.7 percent of those who received weekly paclitaxel plus placebo. There was no significant difference in the quality of life.