The FDA has approved ribociclib combined with aromatase inhibitor therapy for women with metastatic HR-positive, HER2-negative breast cancer. It is the second CDK 4/6 inhibitor approved for these patients, behind palbociclib; a third is under investigation.

The FDA has approved the CDK 4/6 inhibitor ribociclib (Kisquali; Novartis), combined with hormonal therapy, for first-line treatment of postmenopausal women with metastatic HR-positive, HER2-negative breast cancer. It is the second drug in this class, after palbociclib (Ibrance; Pfizer), to be approved for tumors that become resistant to endocrine therapy; a third, potentially less hematotoxic alternative, abemaciclib (Eli Lilly) is in clinical trials.

Ribociclib was approved based on data from the phase III MONALEESA-2 trial, which found that adding ribociclib to the aromatase inhibitor letrozole led to a 44% improvement in progression-free survival (PFS) after 18 months of treatment (63% compared with 42%). The findings were presented at the European Society for Medical Oncology's 2016 Congress and published in The New England Journal of Medicine.

“Ribociclib is very similar to palbociclib in terms of efficacy,” says Lajos Pusztai, MD, DPhil, chief of Breast Medical Oncology at Yale Cancer Center in New Haven, CT. “This approval broadens the treatment options available for these patients.”

Although both palbociclib and ribociclib have been shown to significantly extend PFS, neutropenia often occurs, leading to dose delays or reductions in more than 70% of patients, he adds. As a result, patients taking the drugs require regular laboratory monitoring.

Abemaciclib may soon offer an alternative. According to data from the phase III MONARCH 2 trial, the combination of abemaciclib plus fulvestrant (Faslodex; AstraZeneca) significantly improved PFS compared with fulvestrant alone in women with advanced disease—with fewer incidences of dose-limiting neutropenia, but more frequent diarrhea. Eli Lilly plans to release more details and submit data to the FDA for review later this year.

“Abemaciclib has a different chemical structure, greater selectivity for CDK4, and a substantially different side effect and efficacy profile than the currently approved agents,” says Pusztai. “However, we don't yet know how to optimally dose CDK 4/6 inhibitors so that they are the least toxic while preserving efficacy.” –Janet Colwell

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.