MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy.

By G. Sledge, Masakazu Toi, Patrick Neven, J. Sohn, Kenichi Inoue, X. Pivot, O. Burdaeva, M. Okera, N. Masuda, P. Kaufman and 8 more. Journal of Clinical Oncology, 2017

1,439 citations recorded by the source corpus.

Purpose MONARCH 2 ( ClinicalTrials.gov identifier: NCT02107703) compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, plus fulvestrant with fulvestrant alone in patients with advanced breast cancer (ABC). Patients and Methods MONARCH 2 was a global, double-blind, phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy (ET), ≤ 12 months from the end of adjuvant ET, or while receiving first-line ET for metastatic disease. Patients were randomly assigned 2:1 to receive abemaciclib or placebo (150 mg twice daily) on a continuous schedule and fulvestrant (500 mg, per label). The primary end point was investigator-assessed progression-free survival (PFS), and key secondary end points included overall survival, objective response rate (ORR), duration of response, clinical benefit rate, quality of life, and safety. Results Between August 2014 and December 2015, 669 patients were randomly assigned to receive abemaciclib plus fulvestrant (n = 446) or placebo plus fulvestrant (n = 223). Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone (median, 16.4 v 9.3 months; hazard ratio, 0.553; 95% CI, 0.449 to 0.681; P < .001). In patients with measurable disease, abemaciclib plus fulvestrant achieved an ORR of 48.1% (95% CI, 42.6% to 53.6%) compared with 21.3% (95% CI, 15.1% to 27.6%) in the control arm. The most common adverse events in the abemaciclib versus placebo arms were diarrhea (86.4% v 24.7%), neutropenia (46.0% v 4.0%), nausea (45.1% v 22.9%), and fatigue (39.9% v 26.9%). Conclusions Abemaciclib at 150 mg twice daily plus fulvestrant was effective, significantly improving PFS and ORR and demonstrating a tolerable safety profile in women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who progressed while receiving ET.

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/a8bebd80fe4d66c86cc44f1cd06a1836a4ebc490

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Oncology

Citations in the corpus

4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)† (2018, background): “In the second-line setting, their use has been associated with a 6–7 months progression-free survival (PFS) benefit [33, 34] and an HRQoL improvement [35, 36], and hence their ESMO-MCBS score is 4.”
5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5) (2020, background): “The last 2 years have seen the establishment of cyclindependent kinase (CDK)4/6 inhibitors combined with endocrine therapy (ET) as the standard of care for ER-positive/HER2-negative ABC in view of the OS benefit seen in several trials,(36-42) both in the first- and second-line settings, substantial ”
Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE) (2020, neutral): “This intriguing observation has been reported previously in a randomized study of a CDK4/6 inhibitor plus ET.20 The most frequently reported AE in the abemaciclib arm was diarrhea.”