Early Results of an Oral CDK4/6 Inhibitor, Abemaciclib, Prove Mixed

A phase 1 study in 225 patients diagnosed with breast cancer, non-small cell lung cancer, glioblastoma, melanoma, or colorectal cancer has concluded that abemaciclib, a selective inhibitor of the cell cycle regulators CDK4/6, has single-agent activity in specific tumor types.

A phase 1 study in 225 patients diagnosed with breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, melanoma, or colorectal cancer (CRC) has concluded that abemaciclib, a selective inhibitor of the cell cycle regulators CDK4/6, has single-agent activity in specific tumor types.

Another CDK4/6 inhibitor, palbociclib, which was approved as frontline treatment for postmenopausal women with ER-positive and HER2-negative breast cancer in 2015, was recently granted an extended indication in combination with fulvestrant for ER-positive/HER2 negative breast cancer patients whose disease has progressed.

Geoffrey I. Shapiro, MD, PhD, director of the Early Drug Development Center at the Dana-Farber Cancer Institute, and a senior author on the abemaciclib study, explained the difference between the 2 drugs. Abemaciclib has “distinct attributes that contribute to its discrete therapeutic effects, in particular, its single-agent activity,” Shapiro said in a statement. “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.”

In the current study, 33 patients were a part of the dose escalation study and 192 patients were included in tumor-specific cohorts for breast cancer (47), NSCLC (68), glioblastoma (17), melanoma (26), CRC (15), and hormone-positive breast cancer (19). A majority of trial participants had at least 2 metastatic sites and had received multiple prior treatments. The most common adverse events following treatment included fatigue, diarrhea, nausea, vomiting, anorexia, weight loss, kidney dysfunction, and decreased red and white blood cell counts.

Radiographic responses were observed for some patients with breast cancer, NSCLC, and melanoma. Of 36 patients with hormone receptor—positive breast cancer, 11 had a partial response and 18 patients had stable disease. Two out of 68 patients with NSCLC who were treated with single-agent abemaciclib had a partial response, and 31 had stable disease. Among the melanoma patients, 1 had a partial response and 6 had stable disease. Three of 17 patients with glioblastoma had stable disease, and 2 of them continued their treatment without disease progression for 19 and 23 cycles.

The authors recommend the need to follow up with confirmatory clinical trials that would include more homogenous patient populations with a specific tumor type. “Multiple clinical trials have already been initiated to evaluate abemaciclib as a treatment for certain groups of patients with breast cancer and NSCLC, as well as children with primary brain tumors and adults with brain metastases,” said Amita Patnaik, MD, associate director of clinical research at South Texas Accelerated Research Therapeutics, who’s also a senior author on the paper.

Reference

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 Discov. doi:10.1158/2159-8290.CD-16-0095.