The oral drug LY2835219, an inhibitor of cyclin-dependent kinases 4 and 6, showed some benefit as monotherapy for patients with metastatic breast cancer, particularly for those with hormone receptor–positive disease, in a phase I trial.
According to results of a phase I study, the oral drug LY2835219, an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, showed some benefit as monotherapy for patients with metastatic breast cancer, particularly for those with hormone receptor (HR)–positive disease. The findings were presented at the American Association of Cancer Research Annual Meeting 2014 in San Diego, CA, on April 6.
“Preclinical evaluation indicated that LY2835219 may have a potential therapeutic application for the treatment of human cancers in which aberrant CDK4/6 pathway enhances cancer cell growth,” said Amita Patnaik, MD, associate director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio.
Based on those results, Patnaik and her colleagues tested LY2835219 as a single-agent therapy in 132 patients with glioblastoma multiforme, melanoma, or non–small cell lung, colorectal, or breast cancers. She reported the results of only the breast cancer arm of the trial, which included 47 patients with metastatic disease, 36 of whom were HR-positive.
All of the patients were heavily pretreated, explained Patnaik, noting that they had received a median of seven prior therapies and were no longer deriving any clinical benefit from other drugs. They were given LY2835219 twice a day in 28-day cycles, a schedule they followed until their tumors progressed or they developed unacceptable side effects.
Overall, Patnaik said, nine patients (19%) had a partial response, 24 (51%) had stable disease, 11 experienced disease progression, and three could not be evaluated for a response. All of the patients who had a partial response, as well as 20 of the 24 who had stable disease, had HR-positive disease. The disease control rate, defined as the sum of complete and partial responses and stable disease, was 81% for those with HR-positive disease. About 80% of breast cancers are HR-positive.
Patnaik estimated progression-free survival to be 9.1 months among HR-positive patients, but she said that could change because 18 patients were still taking LY2835219 when the data were analyzed.
“Although our study was not designed to compare patient outcomes based on HR status, the clinical benefit rate was 61% in our patients with HR-positive breast cancer, which means patients had disease control for longer than 24 weeks or had their tumors reduced in size by more than 30%,” Patnaik explained. “This is very encouraging, and warrants the initiation of future clinical trials in this setting where treatments are needed.”
Another encouraging sign, Patnaik said, was that none of the breast cancer patients dropped out of the trial due to side effects. The most common adverse events related to treatment included diarrhea, nausea, fatigue, neutropenia, vomiting, and decreased platelet and white-blood cell counts.