Novel Combination Therapy Studied in Endometrial, Ovarian, and Breast Cancers
Posted: Friday, July 6, 2018
Combination therapy with the PARP inhibitor olaparib plus the mTORC1/2 inhibitor vistusertib seemed to be well tolerated with “durable antitumor activity” when used in the treatment of patients with recurrent endometrial, ovarian, and triple-negative breast cancers, according to phase I study findings presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 5504). Shannon Neville Westin, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues concluded that “promising response was seen in both histologies of endometrial cancer.”
In this early-phase trial, 74 patients, 8 with BRCA mutations, were enrolled. They received oral schedules for vistusertib twice daily. Arm one received continuous treatment (five dose levels) twice daily, whereas arm had treatment twice daily orally (four dose levels) for 2 days on followed by 5 days off.
Of the 64 evaluable patients, the response rate across all dose levels was 19%, with a medium duration of 14 months and a clinical benefit rate of 34%. Dr. Westin and colleagues observed a 27% response rate in endometrial cancer, 20% in ovarian cancer, and 6% in breast cancer. For the 49 evaluable patients within the arm two cohort, response and clinical benefit rates were 19% and 37%, respectively. Also in arm two, the response rate was 31%, 15%, and 8% in endometrial, ovarian, and breast cancers, respectively.
Two dose-limiting toxicities were observed in the first arm, and three dose-limiting toxicities were reported on the second arm. The most common adverse events were nausea (84%), anemia (83%), hyperglycemia (76%), and fatigue (73%).
