Dr. Gogineni on the Efficacy of CDK4/6 Inhibitors Plus Endocrine Therapy in HR+, HER2- Early Breast Cancer

Keerthi Gogineni, MD, MSHP, an assistant professor of the Department of Hematology and Medical Oncology, and associate director of the Hematology and Medical Oncology Fellowship Program at Emory University School of Medicine, as well as the director for Education of Fellows and Residents at Grady Health System, discusses the efficacy of CDK4/6 inhibitors plus endocrine therapy in patients with hormone receptor–positive, HER2-negative early breast cancer.

Experts in the field have been satisfied with outcomes observed with this combination in terms of progression-free survival, and even overall survival in the advanced setting, Gogineni says. Due to this, investigators set out to determine whether the combination would decrease the risk of recurrence for women who have higher-risk, early-stage breast cancer. 

Thus far 3 trials have read out in 2021 regarding CDK4/6 inhibition in the early-stage setting. In 2 of the studies that involved the use of palbociclib (Ibrance), despite enrolling a high-risk patient population, investigators reported no additional benefits from using palbociclib with endocrine therapy.

There are a handful of reasons that may account for these results, Gogineni explains. In the phase 3 PENELOPE-B study (NCT01864746), the duration of palbociclib may have been too short at 1 year of therapy, she says. Moreover, in the phase 3 PALLAS trial (NCT02513394), investigators noted high discontinuation rates in the treatment arm. Benefit may not have been observed because many patients were not able to continue treatment with palbociclib.

With respect to risk, and in comparison to the phase 3 monarchE trial (NCT03155997) which used abemaciclib with the same strategy, another issue was that despite being high-risk, the patients enrolled on PENELOPE-B and PALLAS were less high-risk than those enrolled on monarchE. This could indicate that patients need to be carefully selected in order to ensure they will respond best to this strategy, Gogineni concludes.