Abemaciclib, a selective cyclin-dependent kinase (CDK) 4 and 6 inhibitor, plus fulvestrant significantly improved the progression-free survival (PFS) and increased the objective response rate (ORR) in women with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer.1,2 These results, from the MONARCH 2 study, were simultaneously presented at the American Society of Clinical Oncology (ASCO) Annual meeting1 and published in the Journal of Clinical Oncology.2
Abemaciclib plus fulvestrant significantly extended PFS compared with fulvestrant alone (median, 16.4 and 9.3 months, respectively; hazard ratio, 0.553; 95% confidence interval [CI], 0.449–0.681; p
The combination of abemaciclib plus fulvestrant was associated with more toxicity than fulvestrant alone; this included diarrhoea, neutropenia, nausea, fatigue, abdominal pain, anaemia, leukopenia, decreased appetite, and vomiting. The most common adverse events in the abemaciclib plus fulvestrant versus fulvestrant arms were diarrhoea (86.4% versus 24.7%), neutropenia (46.0% versus 4.0%), nausea (45.1% versus 22.9%), and fatigue (39.9% versus 26.9%).
“Abemaciclib plus fulvestrant was an effective treatment for women with hormone receptor-positive, HER2-negative advanced breast cancer whose disease progressed on prior endocrine therapy," said lead author, George Sledge, MD, of Stanford University at the ASCO Annual Meeting. "Abemaciclib dosed on a continuous schedule was generally well tolerated."
Sledge added that, on the basis of these promising findings in advanced disease, a randomized trial of abemaciclib and endocrine therapy in the adjuvant setting will start enrolment late-2017.
Abemaciclib is an oral, potent and selective small-molecule inhibitor of CDK 4 and 6.3-5 In MONARCH I, a phase II study, single agent abemaciclib in patients with HR positive/HER2-negative metastatic breast cancer, the overall response rate was 19.7%, median duration of response was 8.6 months, and the clinical benefit rate (complete response plus partial response plus table disease ≥6 months) was 42.4%.3 Abemaciclib was administered in MONARCH 1 at a dosage of 200 mg twice daily on a continuous schedule and, in MONARCH 2, at 150 mg twice daily on a continuous schedule.
MONARCH 1 and 2 were supported by Eli Lilly & Co. Abemaciclib is also being investigated for a range of other cancer types including lung and pancreatic cancer and brain metastases.
1. Sledge G, 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; abstr 1000).
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 Progressed While Receiving Endocrine Therapy, J Clin Oncol, 2017;Jco2017737585.
3. Dickler MN, Tolaney SM, Rugo HS, et al:, MONARCH1: Results from a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease, J Clin Oncol, 2016;34:(suppl; abstr 510).
4. Patnaik A, Rosen LS, Tolaney SM, et al., Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors, Cancer Discov, 2016;6:740-53.
5. Gelbert LM, Cai S, Lin X, et al., Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine, Invest New Drugs, 2014;32:825-37.