5/23/2016 PHILADELPHIA — The investigational anticancer therapeutic abemaciclib, which targets CDK4 and CDK6, showed durable clinical activity when given as continuous single-agent therapy to patients with a variety of cancer types, including breast cancer, non–small cell lung cancer (NSCLC), glioblastoma, and melanoma, according to results from a phase I clinical trial published in Cancer Discovery, a journal of the American Association for Cancer Research.Amita Patnaik

The results of the trial supported the U.S. Food and Drug Administration (FDA) decision to grant breakthrough therapy designation to abemaciclib (previously known as LY2835219) for patients with refractory hormone receptor–positive advanced or metastatic breast cancer, according to one of the senior authors of the study, Amita Patnaik, MD, associate director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio, Texas.

In February 2015, the FDA approved the CDK4/6 inhibitor palbociclib (Ibrance) for use in combination with the aromatase inhibitor letrozole for treating postmenopausal women with estrogen receptor–positive, HER2-negative advanced breast cancer.
“Abemaciclib, an oral CDK4/6 inhibitor, is a very different molecule from palbociclib, with distinct attributes that contribute to its discrete therapeutic effects, in particular, its single-agent activity,” said the other senior author of the study, Geoffrey I. Shapiro, MD, PhD, director of the Early Drug Development Center at the Dana-Farber Cancer Institute in Boston. “For example, abemaciclib has greater selectivity for CDK4 compared with palbociclib, which may explain why it does not affect white blood cell counts as severely, allowing it to be taken on a continuous schedule without treatment holidays. Abemaciclib also penetrates the central nervous system, whereas palbociclib does not, raising the possibility that it could be used to treat primary or metastatic brain tumors.”Geoffrey Shapiro

Patnaik, Shapiro, and colleagues enrolled 225 patients with a variety of types of advanced cancer in the phase I clinical trial designed to evaluate the safety and preliminary efficacy of abemaciclib. In the dose escalation phase, the researchers determined that the maximum tolerated dose was 200 milligrams (mg) every 12 hours; the dose-limiting toxicity was grade 3 fatigue.

In the expansion phase, single-agent abemaciclib was administered to 47 patients with breast cancer, 68 with NSCLC, 17 with glioblastoma, 26 with melanoma, and 15 with colorectal cancer. Among these patients, the most common treatment-related adverse events were fatigue, diarrhea, nausea, vomiting, anorexia, weight loss, kidney dysfunction, and decreased red and white blood cell counts.

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