Dr Kalinsky on Differences in Efficacy Between CDK4/6 Inhibitors in HR+/HER2- Breast Cancer

Kevin Kalinsky, MD, MS, associate professor, the Department of Hematology and Medical Oncology, Emory University School of Medicine, director, the Glenn Family Breast Center, Breast Medical Oncology, Louisa and Rand Glenn Family Chair in Breast Cancer Research, Winship Cancer Institute of Emory University, discusses differences in efficacy data for CDK4/6 inhibitors in the treatment of patients with metastatic hormone receptor (HR)–positive/HER2-negative breast cancer.

Although the CDK4/6 inhibitors palbociclib (Ibrance), ribociclib (Kisqali) and abemaciclib (Verzenio) are all approved by the FDA for the treatment of patients with metastatic HR-positive/HER2-negative breast cancer, efficacy outcomes of different trials have been inconsistent in the metastatic setting, Kalinsky begins.

The final analyses of both the phase 3 MONALEESA-2 (NCT01958021) and the MONALEESA-3 (NCT02422615) trials confirmed the progression-free survival and overall survival (OS) benefits for ribociclib when added to hormonal therapy. However, the phase 3 PALOMA-2 trial (NCT01740427) of palbociclib plus letrozole (Femara) did not meet its OS end point in postmenopausal women with HR-positive/HER2-negative advanced breast cancer. Data from the phase 3 MONARCH 3 trial (NCT02246621) showed that data for abemaciclib plus letrozole or anastrozole (Arimidex) trended toward a benefit in OS vs letrozole or anastrozole alone, but the results did not reach statistical significance.

There is ongoing debate regarding a potential explanation for these inconsistencies, including whether they can be attributed to variable study design or inherent mechanistic differences, Kalinsky continues. Several potential explanations have been proposed that also acknowledge and account for the danger of conducting cross-trial comparisons, Kalinsky notes. A lack of consistent follow-up of the control group in PALOMA-2 could greatly contribute to discrepancies, he says. Moreover, differences in the length of a patient’s disease-free interval in PALOMA-2 may suggest that patients experienced earlier disease recurrence, Kalinsky concludes.