A recent phase III trial demonstrated that initial therapy with an immuno-agent improves progression-free survival (PFS) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer, published in the Journal of Clinical Oncology (online October 2, 2017; doi:10.1200/JCO.2017.75.6155).
Monotherapy with abemaciclib—an orally-administered cyclin-dependent kinase 4 and 6 inhibitor—has previously shown effectiveness in improving outcomes among patients with endocrine therapy-refractory disease. However, the drug’s effect in combination with nonsteroidal aromatase inhibitors has yet to be studied.
Matthew P Goetz, MD, Mayo Clinic (Rochester, MN), and colleagues conducted a trial to evaluate the safety and efficacy of abemaciclib plus a nonsteroidal aromatase inhibitor vs placebo plus an aromatase inhibitor among patients with HR+, HER2- breast cancer. A total of 493 postmenopausal patients who had no prior systemic therapy in the advanced setting were randomly assigned (2:1) to either the abemaciclib arm (150 mg twice daily) or the placebo arm. All patients received either anastrozole (1 mg) or letrozole (2.5 mg) daily as their nonsteroidal aromatase inhibitor.
The primary objective of the study was investigator-assessed PFS. Secondary objectives included objective response and safety.
Results of the study showed that patients in the abemaciclib arm had a longer median PFS than those in the placebo arm (not reached vs 14.7 months, respectively; HR, 0.54; P = .000021). Patients who demonstrated measurable disease also had a higher objective response with abemaciclib (59%0 than with placebo (44%). A total of five complete responses were observed in the abemaciclib arm compared with zero complete responses in the placebo arm.
Researchers acknowledged that the rate of serious adverse events was higher in the abemaciclib arm (27.5%) than in the placebo arm (14.9%). Eight patients in the abemaciclib arm died due to adverse events, compared with two patients in the placebo arm.
Researchers concluded that despite their data not yet being mature, abemaciclib plus a nonsteroidal aromatase inhibitor provides an effective initial therapy regimen in patients with HR+, HER2- advanced breast cancer. Furthermore, the therapy regimen offers a tolerable safety profile in this population.—Zachary Bessette