Dr Ali on the Efficacy of CDK4/6 Inhibition in ER+, HER2+ Breast Cancer

“Agents like CDK4/6 inhibitors—palbociclib specifically, which is what [was] used in PATINA—are going to improve disease outcomes in those patients who [have] HER2-positive [disease] that is also ER [positive].”

Azka Ali, MD, a medical oncologist in the Department of Hematology and Medical Oncology at the Cleveland Clinic Taussig Cancer Institute, discussed clinical trial data that have informed the role of CDK4/6 inhibition in patients with estrogen receptor (ER)–positive breast cancer, including those with HER2-positive disease.

Both the phase 3 monarchE (NCT03155997) and PATINA (NCT02947685) trials have helped guide the use of CDK4/6 inhibitors for patients with several breast cancer subtypes. The monarchE trial investigated adjuvant abemaciclib (Verzenio) plus endocrine therapy in patients with ER-positive, HER2-negative, high-risk early breast cancer. This trial showed that 2 years of adjuvant abemaciclib plus endocrine therapy improved invasive disease–free survival, distant relapse–free survival, and overall survival in this population compared with endocrine therapy alone.

In contrast, the PATINA trial evaluated palbociclib plus standard-of-care maintenance therapy in patients with ER-positive, HER2-negative breast cancer. PATINA showed that the addition of palbociclib to first-line maintenance anti-HER2 and endocrine therapy following induction chemotherapy resulted in a statistically significant and clinically meaningful progression-free survival (PFS) improvement compared with anti-HER2 therapy and endocrine therapy alone in this patient population. The median PFS was 44.3 months (95% CI, 32.4-60.9) in the palbociclib arm vs 29.1 months (95% CI, 23.3-38.6) in the control arm (HR, 0.74; 95% CI, 0.58-0.94; unstratified 1-sided P = .0074).

The findings from these 2 trials collectively suggest that CDK4/6 inhibitors play a significant role in the management of ER-positive breast cancer, and that this role is likely independent of HER2 status, according to Ali. In HER2-positive breast cancer, targeting the HER2 pathway with monoclonal antibodies remains essential for disease control, she explained. However, the results from PATINA indicate that CDK4/6 inhibitors—specifically palbociclib—may further enhance clinical outcomes in patients with both HER2-negative and ER-positive disease, she concluded.