Abemaciclib, Nonsteroidal Aromatase Inhibitor Extends Overall Survival for Patients With HR+, HER2- Advanced Breast Cancer

Final overall survival (OS) data from the MONARCH 3 study (NCT02246621) showed that the combination of abemaciclib (Verzenio; Lilly) and a nonsteroidal aromatase inhibitor (NSAI) as first-line therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer resulted in numerically longer OS compared to an NSAI alone, although it did not meet statistical significance. The data were presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) in Texas.

MONARCH 3 is a randomized, double-blind, phase 3 study of abemaciclib plus an NSAI (anastrozole or letrozole) vs placebo plus an NSAI in postmenopausal women with HR-positive, HER2-negative advanced breast cancer without prior systemic therapy in the advanced setting. OS was a gated secondary endpoint and chemotherapy-free survival was an exploratory endpoint.

Presenter Matthew Goetz, MD, an oncologist at Mayo Clinic, noted that there have been 2 previous interim analyses of OS and this is the final data. “The previously demonstrated [progression-free survival (PFS)] benefit that we had published persists,” Goetz said.

A total of 493 women were randomly assigned 2:1 to receive abemaciclib plus an NSAI (n=328) or placebo plus an NSAI (n=165). After a median follow-up of 8.1 years, 7% of patients were still receiving treatment in the abemaciclib arm versus 3% in the placebo arm. In the intent-to-treat (ITT) population, 314 OS events were observed, including 198 deaths among 328 patients (60%) in the abemaciclib arm and 116 deaths among 165 patients (70%) in the placebo arm (HR=0.804).

The median OS was 66.8 months in the abemaciclib arm vs 53.7 months in the placebo arm, a numerical difference of 13.1 months in the ITT population. In the subgroup with visceral disease, 178 events were observed, including 113 deaths among 173 patients (65%) in the abemaciclib arm and 65 deaths among 90 patients (72%) in the placebo arm (HR=0.758).

“With a median follow-up of a little over 8 years, abemaciclib in combination with an [aromatase inhibitor] resulted in numerically longer survival compared to an [aromatase inhibitor] alone,” Goetz said. “However, statistical significance was not reached.”

In the subgroup with visceral disease, median OS was 63.7 months in the abemaciclib arm and 48.8 months in the placebo arm, with a numerical difference of 14.9 months. Consistent OS differences were observed across prespecified subgroups and PFS benefit was sustained (median 29 vs 14.8 months; HR, 0.535) with substantial difference in 6-year PFS rates (23.3% vs 4.3% for abemaciclib vs placebo, respectively).

In the subgroup with visceral disease, median OS was 63.7 months in the abemaciclib arm and 48.8 months in the placebo arm, with a numerical difference of 14.9 months. Image Credit: © Kanisorn - stock.adobe.com

Investigators also noted that chemotherapy-free survival improved with abemaciclib vs placebo (median 46.7 vs 30.6 months; HR, 0.693). No new safety signals were observed with longer term use.

“These data really are consistent with the totality of the data demonstrated with abemaciclib in the adjuvant as well as the neoadjuvant setting,” Goetz said during the presentation.

Goetz pointed out that this was the smallest of all the CDK4/6 trials with just 493 patients, and the ability to examine survival was also limited by 2:1 randomization.

“I think as we look at these data, we have to acknowledge that it’s not statistically significant,” Goetz said. “But we need to interpret it, obviously, in light of those caveats.”

Reference

Goetz M. MONARCH 3: Final overall survival results of abemaciclib plus a nonsteroidal aromatase inhibitor as first-line therapy for HR+, HER2- advanced breast cancer. Presented at: San Antonio Breast Cancer Symposium. December 5-9, 2023.