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

Abstract

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.

Gastrointestinal adverse effects of cyclin-dependent kinase 4 and 6 inhibitors in breast cancer patients: a systematic review and meta-analysis

“…In concordance with our findings, addition of abemaciclib was associated with significant increase in the risk of all-grade diarrhea, nausea and vomiting. 25 However, our analysis has some potential weaknesses and results should be taken cautiously. First, the GI toxicities might be caused by some of the concomitant medications/diseases that patients with metastatic breast cancer might use/suffer from.…”

Hormone Receptor–Positive, HER2-Negative Metastatic Breast Cancer: Redrawing the Lines

“…Table ii summarizes the most relevant data for postmenopausal patients in the second-line setting. Table ii lists combination trials of cdk 4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) with endocrine therapy in the second-line setting [30][31][32]41 .…”

“…Abemaciclib was studied in the phase iii monarch 2 trial, which enrolled women with hr-positive, her2-negative advanced breast cancer who progressed while receiving neoadjuvant or adjuvant endocrine therapy, at 12 months or fewer from end of adjuvant endocrine therapy, or on first-line endocrine therapy for mbca and who had not received chemotherapy for metastatic disease 32 . Patients were stratified by metastatic site (visceral, bone only, or other) and resistance to prior endocrine therapy (primary vs. secondary).…”

Endocrine Therapeutic Strategies for Patients with Hormone Receptor-positive Advanced Breast Cancer

“…42 This compound has been investigated in combination with endocrine therapy, in two hazard ratio, 0.553; 95% CI, 0.449 to 0.681; p<0.001). 43 Unlike CDK4/6 inhibitors palbociclib and ribociclib, the most common adverse event in the abemaciclib arm was diarrhoea (86.4%), followed by neutropaenia (46.0%), nausea (45.1%) and fatigue (39.9%).…”