Adjuvant CDK4/6 inhibitors have expanded treatment options for patients with HR+/HER2- early-stage breast cancer, with phase 3 trials supporting benefit when added to endocrine therapy in appropriately selected patients. Ian Krop, MD, PhD, compares the characteristics of candidates for abemaciclib therapy vs ribociclib therapy and outlines practical toxicity monitoring and management strategies to keep treatment tolerable and individualized.

There are 2 definitive phase 3 trials investigating adjuvant CDK4/6 inhibitors (ie, monarchE and NATALEE) that showed that adding either abemaciclib or ribociclib to endocrine therapy, with or without chemotherapy, in patients with HR+/HER2- early-stage breast cancer is associated with substantial benefit and relatively manageable toxicity.

The monarchE trial looked at a high-risk population (ie, patients with ≥4 positive axillary lymph nodes or 1-3 positive axillary lymph nodes and other high-risk features), whereas the NATALEE trial included both high-risk patients and a cohort of node-negative patients who had some high-risk features. Even though the patient populations differed in these 2 trials, the invasive disease-free survival efficacy outcomes looked remarkably similar. Consistent with findings from monarchE and NATALEE showing which individuals received treatment and showed benefit, I offer abemaciclib to high-risk patients and ribociclib to both high-risk patients and node-negative patients who have high-risk features.

What may trigger us to select one drug over the other largely comes down to toxicity and patient preference. Abemaciclib has a risk of diarrhea, which is relatively common. For example, approximately 82% of patients had some degree of diarrhea in monarchE. However, antidiarrheals work quite well, and most patients find this to be a manageable problem. Neutropenia was also common in monarchE (approximately 45%), but serious neutropenia (grade 3 or 4) was less common (approximately 19%). Alternatively, in NATALEE, approximately 44% of patients receiving ribociclib had grade 3 or higher neutropenia. Ribociclib was also associated with potential hepatic toxicity, with approximately 9% of patients having grade 3 or higher liver toxicity. Along with monitoring transaminase elevations, monitoring and addressing other potential contributors to hepatic toxicity are ways to mitigate this. For all these toxicities, dose reductions or discontinuations are ultimately the way to manage these side effects.

Ribociclib is also associated with QTc prolongation in a small fraction of patients. The only way to mitigate this toxicity is to ensure that the patient is not on another drug that prolongs QTc. If they are, then discontinuing that drug or switching to a different drug is a way to address that.

Finally, you can start with one CDK4/6 inhibitor, and, if the patient is having significant problems, you can switch to another drug (in most cases). Considering all these toxicities, there are certain patients who are better candidates for one drug vs the other. For example, it would make sense to avoid abemaciclib in patients who have underlying gastrointestinal problems. Similarly, patients with underlying hepatic toxicity, hepatic dysfunction, prolonged QTc levels at baseline, or depressed levels of neutrophils would be better served with abemaciclib.

Otherwise, for those patients who are candidates for both drugs, it comes down to patient preference. Another factor that patients may consider is the duration of treatment. Ribociclib is a 3-year course, and abemaciclib is a 2-year course. This is something that merits an in-depth discussion so patients can ensure that their preferences are being addressed.