Early Findings Indicate Vistusertib Plus Anastrozole Improved Survival in HR+ Advanced Endometrial Cancer

Eight-week progression-free rate (PFR), overall response rate (ORR), and progression-free survival (PFS) were improved with the addition of vistusertib (AZD2014) to anastrozole (Arimidex) for patients with hormone receptor–positive recurrent or metastatic endometrial cancer, according to results from the phase 1/2 VICTORIA trial (NCT02730923) published in JAMA Oncology.

In the combination arm, the 8-week PFR was 67.3% (unilateral 95% CI, 54.7%) vs 39.1% (unilateral 95% CI, 22.2%) in the anastrozole arm. The investigator-assed 8-week PFR was 69.4% (unilateral 95% CI, 56.8%) in the combination arm and 45.8% (unilateral 95% CI, 28.2%) in the anastrozole arm. The ORR in the combination arm and the anastrozole arm was 24.5% (95% CI, 13.3%-38.9%) vs 17.4% (95% CI, 5.0%-38.8%). At the median follow-up of 27.7 months, the median PFS was 5.2 months (95% CI, 3.4-8.9) in the combination arm and 1.9 months (95% CI, 1.6-8.9) in the anastrozole arm. The median duration of treatment was 3.4 months vs 2.9 months in the combination and anastrozole arms, respectively.

A total of 75 patients enrolled, of whom 73 were eligible for treatment. The median age was 70 years, and race and ethnicity were not collected based on the laws in France. Additionally, 45% of patients were obese or overweight with a body mass index of 30 or higher. Sixty percent of patients had grade 1 and 2 tumors, and 19% of patients had grade 3 and 81% had grade 4 tumors by the International Federation of Gynecology and Obstetrics criteria at inclusion. A total of 56% of patients received previous chemotherapy received, and 12% had previous endocrine therapy. There were 2 patients in the combination arm who were not eligible for treatment because of pretreatment with anastrozole and the development of diabetes, respectively.

Patients were randomized 2:1 to either the combination arm (n = 51) or the anastrozole arm (n = 24); notably, 1 patient was found to be unevaluable, and the analysis was performed with 23 patients.

Patients received oral vistusertib at 125 mg twice a week plus oral anastrozole at 1 mg daily or the oral anastrozole backbone alone.

A total of 2 of 6 patients in the combination arm experienced grade 3 and 4 lymphopenia as a serious adverse effects (SAEs) at the end of the safety run-in period. After investigators validated that the combination arm was safe, an additional 15 patients were enrolled. By the end of the Simon phase 1 at 8 weeks, 10 of 16 patients had not experienced disease progression and they continued on to stage 2. At data cutoff, 7 patients in the combination arm and 3 in the anastrozole arm were still receiving treatment.

One patient experienced a complete response and 11 had partial responses in the combination arm and 4 partial responses were reported in the anastrozole arm. Nine patients in the combination arm experienced a long response to treatment in the experimental arm with a PFS of 12 months or more vs 7 in the anastrozole arm. Among the 16 long-term responders, the median duration of response was 29.6 months (95% CI, 3.7-39.6) in the combination arm and 7.5 months (95% CI, 5.6-18.3) in the anastrozole arm.

Patients had an overall survival rate of 70.8% (95% CI, 48.4%-84.9%) at 12 months and 53.0% (95% CI, 31.2%-70.8%) at 24 months in the anastrozole arm vs 71.3% (95% CI, 56.4%-81.9%) at 12 months and 38.1% (95% CI, 24.3%-51.7%) at 24 months in the combination arm.

One or more SAEs were reported in 32% of patients in the overall population, including 41% of patients in the combination arm and 22% in the anastrozole arm. The most common nonhematologic AEs in the combination arm were fatigue (69%), nausea (51%), and diarrhea (41%). In the anastrozole arm, the most common nonhematologic AEs were fatigue (29%) and arthralgia (29%). In the combination arm, the most common grade 3 and 4 AEs were lower lymphocyte count (20%), hyperglycemia (12%), and fatigue (8%). Treatment was discontinued in 11 patients in the experimental arm, of whom, 4 permanently discontinued vistusertib.

Reference

Heudel P, Frenel JS, Dalban C, et al. Safety and efficacy of the mTOR inhibitor, vistusertib, combined with anastrozole in patients with hormone receptor-positive recurrent or metastatic endometrial cancer: the VICTORIA multicenter, open-label, phase 1/2 randomized clinical trial. JAMA Oncol. Published online May 12, 2022. doi:10.1001/jamaoncol.2022.1047