Dr Bahadur on the Shift in Frontline CDK4/6 Inhibitor Selection in HR+/ HER2– Breast Cancer Breast Cancer

Shakeela Bahadur, MD, specialist, Breast Medical Oncology, Medical Oncology, Banner MD Anderson Cancer Center, discusses how recent data have informed the selection of approved CDK4/6 inhibitors in the frontline setting for patients with metastatic hormone receptor (HR)–positive, HER2-negative breast cancer.

Palbociclib (Ibrance) was the first CDK4/6 inhibitor to gain accelerated approval by the FDA for the treatment of patients with metastatic HR-positive/HER2-negative breast cancer in 2015, Bahadur begins. This regulatory decision was soon followed by approvals for ribociclib (Kisqali) and abemaciclib (Verzenio) in this space.

Accordingly, palbociclib was a commonly selected treatment option in the first line, Bahadur explains. However, findings from the phase 3 PALOMA-2 trial (NCT01740427) showed that the agent in combination with letrozole (Femara) did not provide a statistically and clinically significant overall survival (OS) benefit vs letrozole alone for postmenopausal patients, Bahadur states.

Conversely, ribociclib was shown to improve OS and progression-free survival in both the phase 3 MONALEESA-2 (NCT01958021) and the MONALEESA-3 (NCT02422615) trials when added to first-line ovarian function suppression, she continues. Interim findings from the phase 3 MONARCH-2 trial (NCT02107703) also demonstrated a positive OS trend with abemaciclib in combination with fulvestrant (Faslodex), Bahadur shares.

These data support ribociclib and potentially abemaciclib as a preferred option for patients with advanced or metastatic breast cancer in the first line over palbociclib. However, palbociclib can still have a role in this setting, depending on whether patients have comorbid conditions and may not respond favorably to ribociclib, Bahadur concludes.