Abemaciclib plus NSAI improves overall survival in HR+, HER2− advanced breast cancer

Combination treatment with abemaciclib and a nonsteroidal aromatase inhibitor (NSAI) as initial therapy, compared with NSAI alone, helps extend survival in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer, results of the MONARCH 3 study have shown.  

However, the clinically meaningful improvement in median overall survival (OS) did not reach statistical significance in the final analysis. 

A randomized, double-blind, phase III study, MONARCH 3 investigated abemaciclib plus NSAI (ie, anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- advanced breast cancer who had not previously received any systemic therapy in the advanced setting. 

Investigator-assessed PFS was the primary outcome, while OS and chemotherapy-free survival (CFS) were a gated secondary endpoint and an exploratory endpoint, respectively. 

Of the 493 women included, 328 received abemaciclib plus NSAI and 165 received placebo plus NSAI. A total of 198 OS events occurred in the abemaciclib arm compared with 116 in the placebo arm (60.4 percent vs 70.3 percent; hazard ratio [HR], 0.804, 95 percent confidence interval [CI], 0.637−1.015; p=0.0664) after a median follow-up of 8.1 years. Median OS was longer with abemaciclib than with placebo (66.8 vs 53.7 months). [Ann Oncol 2024;35:718-727] 

In women with visceral disease, 113 OS events occurred in the abemaciclib arm and 65 in the placebo arm (65.3 percent vs 72.2 percent; HR, 0.758, 95 percent CI, 0.558−1.030; p=0.0757). Finally, the median OS was numerically longer with abemaciclib than with placebo (63.7 vs 48.8 months). 

Safety profile 

The combination treatment demonstrated an acceptable safety profile after the longer follow-up. Low-grade diarrhoea was the most common adverse event, which was treated with antidiarrhoeal medications and dose adjustments without compromising efficacy. The safety findings were consistent with those of previous analyses.  

“After a median follow-up of 8.1 years, the previously demonstrated progression-free survival (PFS) benefit was sustained, median chemotherapy-free survival was substantially improved, and no new safety signals were observed,” said lead study author Dr Matthew P. Goetz, Department of Oncology, Mayo Clinic, US. 

“These data continue to support the ... clinical benefit abemaciclib has demonstrated across the MONARCH program, including as adjuvant therapy in node-positive, high-risk early breast cancer, as initial therapy with aromatase inhibitors for metastatic disease, in combination with fulvestrant following disease progression, and as monotherapy in later lines of therapy,” Goetz added.  

Metastatic disease 

Postprogression survival among patients with HR+, HER2− metastatic breast cancer is relatively long, according to the investigators, and these patients often receive multiple lines of therapy during the metastatic disease course. [Am Soc Clin Oncol Educ Book 2020;40:1-11] 

“In this context, the OS assessment of first-line therapy can take years and potentially be confounded by additional systemic therapies after progression,” the investigators said. 

In the MONARCH 2 study, abemaciclib plus fulvestrant resulted in significant improvements in PFS and OS among women with HR+, HER−, advanced breast cancer with disease progression on previous endocrine therapy. In MONARCH 3, abemaciclib plus NSAI as initial therapy improved PFS. [NPJ Breast Cancer 2019;5:5; J Clin Oncol 2017;35:3638-3646]