Abemaciclib is an investigational cancer therapeutic that now shows durable clinical activity when administered as a continuous single-agent therapy to patients with a variety of solid tumors, according to results of a phase 1 trial with 5 tumor-specific cohorts.1

The first FDA-approved CDK4/6 inhibitor, palbociclib, was approved in February 2015 for use in combination with the aromatase inhibitor letrozole in the treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women.

Abemaciclib differs from palbociclib molecularly, and its distinct attributes contribute to its discrete therapeutic options, explained Geoffrey I. Shapiro, MD, PhD, director of the Early Drug Development Center at the Dana-Farber Cancer Institute in Boston, Massachusetts, and senior author of the study.

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For example, abemaciclib has greater selectivity for CDK4 than palbociclib, which may explain why abemaciclib does not affect white blood cell counts as severely, allowing it to be taken on a continuous schedule without treatment holidays, Shapiro explained. 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.

This phase 1 clinical trial (N = 225 patients), funded by Eli Lilly and Company, was designed to evaluate the safety and preliminary efficacy of abemaciclib in a variety of advanced cancers. In the dose escalation phase, the researchers determined that the maximum tolerated dose was 200 mg every 12 hours; dose-limiting toxicity was grade 3 fatigue.

In the expansion phase, single-agent abemaciclib was administered to 47 patients with breast cancer, 68 with non-small cell lung cancer (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 blood cell and white blood cell counts.

Radiography was used to determine responses. Among the 36 patients with ER-positive breast cancer, 11 had a partial response, 4 of whom continued prior endocrine therapy, and an additional 18 patients had stable disease. Among the 68 patients with NSCLC, 2 had a partial response and 31 had stable disease; of these patients, 1 with a partial response and 12 with stable disease were known to have KRAS-mutant NSCLC. Among the 26 patients with melanoma, 1 had a partial response and 6 had stable disease. Three of the 17 patients with glioblastoma had stable disease, with 2 of them continuing to receive treatment without disease progression for 19 and 23 cycles.

“These data show that abemaciclib is an oral drug that can be taken on a continuous schedule and achieve durable clinical activity against multiple tumors including breast and lung cancers,” said Shapiro.

“The results of the trial supported the 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,” added Amita Patnaik, MD, associate director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio, Texas, and senior author of the study.


1. Patnaik A, Rosen LS, Tolaney SM, et al. Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors [published online May 23, 2016]. Cancer Discovery. doi:10.1158/2159-8290.CD-16-0095.