Abemaciclib/Fulvestrant Combo Improves OS in HR+ Advanced Breast Cancer

Abemaciclib plus fulvestrant improved overall survival in patients with hormone receptor–positive, HER2-negative breast cancer.

Anne White

The combination of abemaciclib (Verzenio) and fulvestrant (Faslodex) demonstrated a statistically significant improvement in overall survival (OS) compared with fulvestrant alone in patients with hormone receptor (HR)—positive, HER2-negative advanced or metastatic breast cancer who were previously treated with endocrine therapy, according to results of a definitive preplanned interim analysis of the phase III MONARCH 2 trial.1

The MONARCH 2 study previously demonstrated a statistically significant improvement in progression-free survival (PFS) in both pre/peri and postmenopausal women, which was the basis for the FDA’s approval of the combination regimen in September 2018. There were no new safety signals observed in the updated MONARCH 2 analysis.

“I believe we must continue to fight this devastating disease because the women who are living with metastatic breast cancer want to do everything they can to lead more fulfilling lives and be there for those who need them most,” said Anne White, president of Lilly Oncology, the manufacturer of Lilly Oncology. “While Verzenio had already shown an impressive benefit for progression-free survival, we are delighted that Verzenio is the first and only CDK4/6 inhibitor in combination with fulvestrant that has significantly extended life for both pre/peri and postmenopausal woman.”

Lilly stated that it plans to present the full findings at an upcoming medical meeting and also submit the data to regulatory authorities.

Abemaciclib is FDA approved for the treatment of patients with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy, in combination with fulvestrant for patients with disease progression following endocrine therapy, and as a single agent for those with disease progression after endocrine therapy and prior chemotherapy in the metastatic setting.

In the double-blind, placebo-controlled, phase III MONARCH 2 trial, 669 patients with HR-positive, HER2-negative metastatic breast cancer who progressed on endocrine therapy were randomized 2:1 to abemaciclib plus fulvestrant or placebo/fulvestrant. Abemaciclib was given at a continuous dosing schedule until disease progression or unacceptable toxicity.

Patients received 500 mg of fulvestrant plus placebo or 150 mg of abemaciclib twice daily. The initial abemaciclib dose was 200 mg twice daily; however, the dose was amended after the first 178 patients were enrolled, due to diarrhea-related toxicity concerns. A GnRH agonist was given to pre/perimenopausal patients.

Patients enrolled had disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting while receiving first-line endocrine therapy for metastatic disease, and patients could not have received chemotherapy or ≥1 line of endocrine therapy for metastatic breast cancer.

Patient characteristics were well-balanced between the 2 arms. Eighty-two percent of patients were postmenopausal, 72% had measurable disease, 56% had visceral disease, and 25% had primary endocrine therapy resistance. Additionally, approximately 60% of patients had received neoadjuvant or adjuvant chemotherapy.

The primary endpoint was PFS, and key secondary endpoints included objective response rate (ORR), OS, and duration of response (DOR).

Earlier results showed that the median PFS was 16.4 months (95% CI, 14.4-19.3) with abemaciclib compared with 9.3 months (95% CI, 7.4-12.7) in the fulvestrant-alone group (HR, 0.553; 95% CI, 0.449-0.681; P <.0000001).2 The ORRs among patients with measurable disease were 48.1% and 21.3% in the abemaciclib and control arms, respectively.

Specifically, the 48.1% ORR in the abemaciclib arm included a complete response (CR) rate of 3.5%; there were no complete responses in the placebo arm. The median DOR was not yet reached in the fulvestrant arm, and was 25.6 months in the placebo arm.

Moreover, the investigator-assessed ORR was 19.7% (95% CI, 13.3%-27.5%), with a median duration of response of 8.6 months. The independently reviewed ORR was 17.4% (95% CI, 11.4%-25.0%) with a median response duration of 7.2 months.

Regarding safety, 86.4% of patients experienced all-grade diarrhea and 13.4% had a grade 3 event. Diarrhea frequency was greatest during the first month of treatment with abemaciclib. Thirty-two percent of patients with grade 2 to 3 diarrhea experienced this event in the first cycle of treatment, in the MONARCH 2 trial. The median time to onset of diarrhea was 6 to 8 days, and the duration ranged from 6 to 11 days. For 13% to 22% of patients, a dose reduction or omission was required for management of diarrhea. Overall, 85% of diarrhea events recovered with supportive treatment.


  1. Lilly’s Verzenio (abemaciclib) Significantly Extended Life in Women with HR+, HER2- Advanced Breast Cancer in MONARCH 2 [news release]. Lilly Oncology. Published July 30, 2019. https://bit.ly/2Zkj9jJ. Accessed July 30, 2019.
  2. Sledge GW, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in patients with HR+/HER2- advanced breast cancer who progressed on endocrine therapy. J Clin Oncol. 2017;35(suppl 15; abstr 1000). doi: 10.1200/JCO.2017.35.15_suppl.100.