In the UK phase II OCTOPUS study reported in JAMA Oncology, Susana Banerjee, MBBS, MA, PhD, and colleagues found that the addition of the dual mTORC1/mTORC2 inhibitor vistusertib to weekly paclitaxel did not improve progression-free survival among patients with platinum-resistant or -refractory ovarian high-grade serous carcinoma (PR-HGSC).
As stated by the investigators, “Patients with platinum-resistant or refractory ovarian high-grade serous carcinoma have a poor prognosis and few therapeutic options. Preclinical studies support targeting PI3K/AKT/mTOR signaling in this setting, and a phase I study of the dual mTORC1/mTORC2 inhibitor vistusertib with weekly paclitaxel showed activity.”
Susana Banerjee, MBBS, MA, PhD
Study Details
The multicenter double-blind trial included 140 patients with PR-HGSC of ovarian, fallopian tube, or primary peritoneal origin. They were randomly assigned between January 2016 and March 2018 to receive oral vistusertib at 50 mg (n = 70) or placebo (n = 70) twice daily on days 1 to 3, 8 to 0, and 15 to 17 in addition to weekly paclitaxel at 80 mg/m2 on days 1, 8, and 15 of 28-day cycles. The primary endpoint was progression-free survival in the intention-to-treat population.
Key Findings
Median follow-up for progression-free survival was 13.5 months. Median progression-free survival was 4.5 months in the combination group vs 4.1 months in the control group (hazard ratio [HR] = 0.84, 80% confidence interval [CI] = 0.67–1.07, P = .18).
Median follow-up for overall survival was 32.1 months. Median overall survival was 9.7 months in the combination group vs 11.1 months in the control group (HR = 1.21, 80% CI = 0.91–1.60).
Response rates were 29% vs 30% on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and 53% vs 54% (adjusted odds ratio = 0.86, 80% CI = 0.55–1.36) on Gynecological Cancer Intergroup combined RECIST version 1.1/CA-125 criteria.
Grade 3 or 4 adverse events occurred in 41.2% of patients in the combination group vs 36.7% of the control group, most commonly lymphopenia (13% vs 9%) and fatigue (9% vs 4%).
The investigators concluded, “In this randomized clinical trial of weekly paclitaxel and dual mTORC1/2 inhibition in patients with PR-HGSC, vistusertib did not improve clinical activity of weekly paclitaxel.”
Dr. Banerjee, of The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by AstraZeneca and others. For full disclosures of the study authors, visit jamanetwork.com.
