Final Analysis of MONARCH 2 Trial Results Confirms Overall Survival Endpoint


The phase 3 clinical trial shows that the 5-year OS for patients with HR+/HER2- advanced breast cancer in the abemaciclib plus fulvestrant group was 41.2% vs 29.2% for the placebo arm.

The final overall survival (OS) analysis of the MONARCH 2 (NCT02107703) trial, with a median follow-up of 6.5 years, showed that the statistically significant benefit previously demonstrated for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) with progression on endocrine therapy (ET) was confirmed and maintained, according to a poster presentation at the San Antonio Breast Conference in Texas on December 8, 2022.1

MONARCH 2 was a double-blind, global, phase 3, placebo-controlled, randomized trial of abemaciclib (Verzenio; Eli Lilly and Company) or a placebo plus fulvestrant (Faslodex; AstraZeneca) for treatment of pre-, peri- or postmenopausal women with cyclin-dependent kinase 4 and 6 inhibitor naïve HR-positive/HER2-negative ABC that progressed during ET. In the trial 669 women were randomized 2:1 to receive abemaciclib or a placebo of 150 mg, twice daily, plus fulvestrant.

Randomization was stratified based on metastasis site (bone, visceral, or other) and resistance to prior ET, primary vs secondary. The median follow-up time was approximately 80 months, and at the time of cutoff, 11% of patients were still receiving the study drug in the abemaciclib group compared with 2% in the placebo group.1

The 5-year OS rate was 41.2% for the abemaciclib group compared with 29.2% for the placebo group, while the 6-year OS rate was 34.7% and 23.7%, respectively.1

The OS benefit was consistent across subgroups, with a numerically greater effect observed among patients with poorer prognoses. The results also demonstrated the safety of abemaciclib with longer-term use.1

And adding abemaciclib to fulvestrant delayed the initiation of chemotherapy, with significant differences in annual chemo-free survival rates: for 3 years, 42% vs 29.3%; for 4 years, 37% vs 18.6%, and for 5 years, 32.4% vs 14.7%.1

Monarch 2 met its primary endpoint of progression-free survival (PFS), but OS and safety were key secondary endpoints, and chemotherapy-free survival was an exploratory endpoint defined as the time from randomization to initiation of chemotherapy or death, whichever occurred earliest.1,2

The Kaplan-Meier (KM) method was used to analyze time-to-event variables. A stratified Cox proportional hazards model was used to estimate treatment effect HR. The prespecified final analysis was planned to occur based on 441 OS events. Data cutoff was March 18, 2022.1

The MONARCH 2 trial showed a statistically significantly benefit in PFS (HR: 0.553; 95% CI: 0.449-0.681; p < 0.001); OS (HR: 0.757; 95% CI: 0.606-0.945; p = 0.01) and a manageable safety profile for abemaciclib plus fulvestrant compared with fulvestrant alone.1

No additional cumulative toxicities or safety risks were identified with longer exposure to abemaciclib, according to the presentation.1


1. Llombart-Cussac A, Masakazu Toi, Neven P, et al. Final overall survival analysis of Monarch 2: a phase 3 trial of abemaciclib plus fulvestrant in patients with hormone receptor-positive HER2-negative advanced breast cancer. Poster presentation. San Antonio Breast Cancer Conference in Texas. December 8, 2022.

2. Lilly announces phase 3 MONARCH 2 breast cancer study of abemaciclib met primary endpoint of progression-free survival. Eli Lilly and Company. News release. March 20, 2017. Accessed December 9, 2022.

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