Dr Mayer on the Use of CDK4/6 Inhibitors in HR+/HER2– Breast Cancer

Erica L. Mayer, MD, MPH, director, Breast Cancer Clinical Research, Dana-Farber and Brigham and Women’s Hospital, institute physician, Dana-Farber Cancer Institute, associate professor, medicine, Harvard Medical School, discusses findings from research investigating CDK4/6 inhibitors in patients with hormone receptor (HR)–positive, HER2-negative breast cancer.

CDK4/6 inhibitors are integral to the management of HR-positive breast cancer, Mayer says. These agents, which were first used in breast cancer approximately 10 years ago, are widely used for patients with advanced or metastatic disease, Mayer explains. Four large, randomized trials have evaluated the efficacy and safety of this drug class in the adjuvant setting: the phase 3 PALLAS (NCT02513394) and Penelope-B (NCT01864746) trials with palbociclib (Ibrance); the phase 3 monarchE trial (NCT03155997) with abemaciclib (Verzenio); and the phase 3 NATALEE trial (NCT03701334) with ribociclib (Kisqali).

PALLAS randomly assigned patients with HR-positive HER2-negative early breast cancer to receive 2 years of adjuvant endocrine therapy with or without palbociclib. At a median follow-up of 31 months, invasive disease–free survival (IDFS) events occurred in 8.8% of patients in the ribociclib arm vs 9.1% of patients in the arm that received endocrine therapy alone.

Penelope-B enrolled patients with HR-positive HER2-negative primary breast cancer who did not achieve a pathological complete response after taxane-containing neoadjuvant chemotherapy and were at high risk of relapse to receive endocrine therapy. Patients were randomly assigned to receive either palbociclib or placebo. At a median follow-up of 42.8 months, palbociclib did not improve IDFS vs placebo when added to endocrine therapy (stratified hazard ratio, 0.93; 95% CI, 0.74-1.17; P = .525).

The monarchE trial investigated standard-of-care endocrine therapy with or without abemaciclib in patients with HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence. At a median follow-up of 42 months (interquartile range, 37-47), the median DFS was not reached in either arm, and investigators reported a sustained IDFS benefit with abemaciclib (hazard ratio, 0.664; 95% CI, 0.578-0.762; nominal P < .0001).

NATALEE evaluated adjuvant ribociclib plus endocrine therapy vs endocrine therapy alone in patients with stage II or III HR-positive HER2-negative early breast cancer at risk for recurrence, including patients with no nodal involvement. At a median follow-up of 34 months, the 3-year IDFS rates were 90.4% with ribociclib vs 87.1% with endocrine therapy alone (hazard ratio, 0.748; 95% CI, 0.618-0.906; P = .0014).

Although the PALLAS and Penelope-B trials did not meet their respective primary end points, positive findings from the NATALEE and monarchE trials indicate the benefit of adding CDK4/6 inhibitors to adjuvant endocrine therapy for patients with higher-risk, HR-positive, HER2-negative breast cancer, Mayer concludes.