Insights From: Hope S. Rugo, MD, UCSF Helen Diller Family Comprehensive Cancer Center; Sara Hurvitz, MD, UCLA Jonsson Comprehensive Cancer Center
Debu Tripathy, MD: Abemaciclib is a CDK inhibitor that’s a little bit different in its biology from palbociclib and ribociclib. It was initially tested in patients who were refractory to multiple endocrine therapies, so in later lines of therapy as a single agent. It’s given on a continuous dosing, not 21 days on and 7 days off, and that actually showed a significant amount of activity, more than we would typically see with a biological therapy in this population. It was approved for that indication, but it was also approved on the basis of the MONARCH-2 study in combination with fulvestrant, so in the second-line setting as well. So, those are the 2 areas in which it’s approved.
So, the MONARCH-1 study was a single arm study that looked at patients who had received multiple lines of hormonal therapy and even cytotoxic therapy, and it showed significant activity, more than we typically see with other biological therapies in this space. That led to the approval or part of the approval in the refractory setting for hormone receptor-positive and HER2-negative breast cancer. The MONARCH-2 study was presented later, and that was in the second-line setting, fulvestrant plus or minus abemaciclib, and that actually showed very similar benefits that we’ve seen with CDK4/6 inhibitors, a doubling of progression-free survival.
Abemaciclib is a drug that we have used for refractory disease, and we have a protocol in which we’re designing to use it in an expanded group of patients who may actually have certain biological characteristics that imply that they will be very sensitive to this drug. The one thing about abemaciclib is its toxicity profile is a little bit different. You have a little more in the way of GI toxicities, but less in the way of hematologic toxicities. It’s given continuously, so there isn’t a cyclical drop in the neutrophil counts as well.