In a French phase I/II trial (VICTORIA) reported in JAMA Oncology, Heudel et al found that the addition of the mTOR inhibitor vistusertib to anastrozole improved outcomes in women with hormone receptor–positive recurrent or metastatic endometrial cancer.

As stated by the investigators, “Endometrial cancer is often hormone-dependent and treated with aromatase inhibitors. The PI3K-AKT-mTOR pathway deregulation observed in endometrial cancer drives hormonal resistance, thus supporting the rationale of combining [an] mTOR inhibitor with endocrine therapy.”

Study Details

In the open-label multicenter trial, 73 patients were randomly assigned 2:1 between April 2016 and October 2019 to receive vistusertib at 125 mg twice daily 2 days per week and anastrozole at 1 mg daily (n = 49) or anastrozole alone (n = 24). The primary efficacy endpoint was progression-free rate at 8 weeks on blinded independent central review.

Progression-Free Rate at 8 Weeks

The progression-free rate at 8 weeks was 67.3% (unilateral 95% confidence interval [CI] = 54.7%) in the combination group vs 39.1% (unilateral 95% CI = 22.2%) in the control group.

Objective response was observed in 12 patients (24.5%, 95% CI = 13.3%–38.9%) in the combination group vs 4 (17.4%, 95% CI = 5.0%–38.8%) in the control group. With a median follow-up of 27.7 months, median progression-free survival was 5.2 months (95% CI = 3.4–8.9 months) vs 1.9 months (95% CI = 1.6–8.9 months), with 6-month rates of 43.6% vs 36.1%. 

Adverse Events

The most common adverse events of any grade in the vistusertib/anastrozole group were fatigue (69% vs 29% in control group), nausea (51% vs 8%), and diarrhea (41% vs 13%). The most common grade 3 or 4 adverse events were lymphopenia (20% vs 8%), hyperglycemia (12% vs 0%), and fatigue (8.0% vs 0%). Vistusertib-related serious adverse events occurred in 11 patients (22%).

The investigators concluded, “This multicenter, open-label, phase I/II randomized clinical trial demonstrated that adding vistusertib to anastrozole improved [the] 8-week progression-free rate, overall response rate, and progression-free survival for patients with endometrial cancer and had manageable adverse events. Identification of molecular subgroups would allow for more precise selection of patients who may be most likely to experience favorable outcomes.”

Pierre Heudel, MD, MSc, of the Department of Medical Oncology, Centre Léon Bérard, Lyon, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by the National Cancer Institute of France. For full disclosures of the study authors, visit jamanetwork.com.