MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR(+)/HER2(-) metastatic breast cancer Journal Article


Authors: Dickler, M. N.; Tolaney, S. M.; Rugo, H. S.; Cortés, J.; Diéras, V.; Patt, D.; Wildiers, H.; Hudis, C. A.; O'Shaughnessy, J.; Zamora, E.; Yardley, D. A.; Frenzel, M.; Koustenis, A.; Baselga, J.
Article Title: MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR(+)/HER2(-) metastatic breast cancer
Abstract: Purpose: The phase II MONARCH 1 study was designed to evaluate the single-agent activity and adverse event (AE) profile of abemaciclib, a selective inhibitor of CDK4 and CDK6, in women with refractory hormone receptor-positive (HR+), HER2- metastatic breast cancer (MBC). Experimental Design: MONARCH 1 was a phase II single-arm open-label study. Women with HR+/HER2- MBC who had progressed on or after prior endocrine therapy and had 1 or 2 chemotherapy regimens in the metastatic setting were eligible. Abemaciclib 200 mg was administered orally on a continuous schedule every 12 hours until disease progression or unacceptable toxicity. The primary objective of MONARCH 1 was investigatorassessed objective response rate (ORR). Other endpoints included clinical benefit rate, progression-free survival (PFS), and overall survival (OS). Results: Patients (n = 132) had a median of 3 (range, 1-8) lines of prior systemic therapy in the metastatic setting, 90.2% had visceral disease, and 50.8% had-3 metastatic sites. At the 12-month final analysis, the primary objective of confirmed objective response rate was 19.7% (95% CI, 13.3-27.5; 15% not excluded); clinical benefit rate (CR+PR+SD-6 months) was 42.4%, median progression-free survival was 6.0 months, and median overall survival was 17.7 months. The most common treatment-emergent AEs of any grade were diarrhea, fatigue, and nausea; discontinuations due to AEs were infrequent (7.6%). Conclusions: In this poor-prognosis, heavily pretreated population with refractory HR+/HER2- metastatic breast cancer, continuous dosing of single-agent abemaciciclib was well tolerated and exhibited promising clinical activity. © 2017 AACR.
Journal Title: Clinical Cancer Research
Volume: 23
Issue: 17
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2017-09-01
Start Page: 5218
End Page: 5224
Language: English
DOI: 10.1158/1078-0432.ccr-17-0754
PROVIDER: scopus
PMCID: PMC5581697
PUBMED: 28533223
DOI/URL:
Notes: Article -- Export Date: 2 October 2017 -- Source: Scopus
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MSK Authors
  1. Clifford Hudis
    837 Hudis
  2. Maura N Dickler
    237 Dickler
  3. Jose T Baselga
    394 Baselga