Risky business.

Top Line: CDK 4/6 inhibitors play an important role in the treatment of advanced, hormone receptor positive, HER2- breast cancer.

The Study: Several trials are also asking whether women with localized breast cancer may also benefit from adjuvant CDK 4/6 inhibition. Recently, the monarchE trial found that 2 years of abemaciclib improved 3-year invasive disease-free survival (iDFS) by 3.5% (88.7 → 92.2%) in women with high risk (mostly LN+) hormone receptor (HR)+ breast cancer. However, the PALLAS trial found no improvement in 3-year iDFS with 2 years of palbociclib (88.2% vs 88.5%). The PENELOPE-B trial sought to determine if 1 year of adjuvant palbociclib could improve iDFS specifically among patients who have high risk, HR+/HER2- residual disease following neoadjuvant chemotherapy. 1250 patients were randomized to standard endocrine therapy +/- 1 year of palbociclib. “High risk of relapse” was defined as a score of ≥3 or a score of 2 and ypN+ using the clinical pathological staging-estrogen receptor grading (CPS-EG) scoring system. There was no significant difference in rate of iDFS at 3 years at 81.2% with palbociclib and 77.7% with placebo. And you’d be correct in noting that the 3.5% difference wasn’t significant in PENELOPE-B, although it enrolled less than a quarter the number of patients in monarchE. You do the math.

TBL: While there may be a benefit from the addition of CDK 4/6 inhibition among select women with high risk localized HR+ breast cancer, ideal patient selection remains elusive. | Loibl, J Clin Oncol 2021