Addition of Abemaciclib to Fulvestrant Improves OS in HR+, HER2- Advanced Breast Cancer

The combined use of a CDK4/6 inhibitor with endocrine therapy yielded a 9.4-month median OS benefit among patients.

Treatment with abemaciclib (Verzenio) in combination with fulvestrant (Faslodex) induced a 9.4-month median overall survival (OS) benefit among patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer who progressed on endocrine therapy, according to results from the MONARCH2 trial published in JAMA Oncology.1

Median OS was 46.7 months with the addition of the CDK4/6 inhibitor to fulvestrant, compared with 37.3 months in those who were given placebo plus endocrine therapy (HR, 0.76; 95% CI, 0.61-0.95; P = .01).

“The MONARCH 2 study demonstrated that the addition of abemaciclib, dosed on a continuous, twice-daily schedule, to fulvestrant resulted in a statistically significant improvement in OS, a key secondary objective of this phase III study,” the researchers wrote.

Moreover, improvement in OS was consistent across all stratification factors; however, this was more pronounced in patients with visceral disease (HR, 0.68; 95% CI, 0.51-0.89) and primary resistance to prior endocrine therapy (HR, 0.69; 95% CI, 0.45-1.04).

Lastly, time to second disease progression (median, 23.1 months vs 20.6 months, respectively), time to chemotherapy (median, 50.2 months vs 22.1 months), and chemotherapy-free survival (median, 25.5 months vs 18.2 months) were also improved with the addition of abemaciclib to fulvestrant, compared with the placebo group.

Of note, no new safety signals were observed with the CDK4/6 inhibitor.

The global, randomized, placebo-controlled double-blind phase III MONARCH 2 is trial evaluated abemaciclib in combination with fulvestrant, a selective estrogen receptor degrader, in 669 women with HR-positive, HER2-negative advanced breast cancer who progressed on endocrine therapy. The researchers randomized patients 2:1 to receive either abemaciclib (n = 446) or placebo (n = 223) in combination with the fulvestrant.

Progression-free survival served as the primary endpoint, which was shown to be significantly extended in a study 2 years ago.2


PFS was significantly improved for those treated with abemaciclib versus placebo (median, 16.4 months vs. 9.3 months, respectively; HR, 0.55; 95% CI, 0.45-0.68; P <.001), as well as improved overall response rates (48.1% vs 21.3%; <.001). 


1. Sledge GW Jr, Toi M, Neven P, et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy‑MONARCH 2. JAMA Oncol. doi:10.1001/jamaoncol.2019.4782.


2. Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had pro0gressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875-2884. doi:10.1200/JCO.2017.73.7585.