As reported in JAMA Oncology by George W. Sledge, Jr, MD, and colleagues, an interim analysis of overall survival in the phase III MONARCH 2 trial has shown a significant advantage for abemaciclib plus fulvestrant vs fulvestrant alone in women with advanced hormone receptor–positive, HER2-negative breast cancer whose disease had progressed after prior treatment with endocrine therapy.

George W. Sledge, Jr, MD

The previously reported primary analysis in the trial showed that abemaciclib plus fulvestrant was associated with significantly improved progression-free survival vs treatment with fulvestrant alone.

Study Details

In the double-blind trial, 669 women of any menopausal status from 142 sites in 19 countries were randomly assigned 2:1 between August 2014 and December 2015 to receive abemaciclib/fulvestrant (n = 446) or placebo/fulvestrant (n = 223). Treatment consisted of abemaciclib at 150 mg or placebo twice daily in each 28-day cycle plus intramuscular fulvestrant at 500 mg on days 1 and 15 of the first cycle and on day 1 of each subsequent cycle, with treatment continuing until disease progression or study withdrawal.

The primary endpoint was investigator-assessed progression-free survival, analyzed from the time of randomization until progressive disease or death. The secondary endpoint of overall survival was analyzed from the time of randomization until death. Exploratory endpoints included time to second disease progression, time to chemotherapy, and chemotherapy-free survival.

Overall Survival

Median follow-up for the current analysis at database lock in June 2019 was 47.7 months. Median overall survival was 46.7 months for patients treated with abemaciclib/fulvestrant vs 37.3 months for patients treated with placebo/fulvestrant (hazard ratio [HR] = 0.757, P = .01).

In subgroup analysis by metastatic sites, hazard ratios were 0.675 (95% confidence interval [CI] = 0.511–0.891) in patients with visceral metastases (n = 373), 0.907 (95% CI = 0.564–1.457) in those with bone-only metastases (n = 180), and 0.928 (95% CI = 0.528–1.632) in those with other metastatic sites (n = 113). In analysis according to endocrine therapy resistance, hazard ratios were 0.686 (95% CI = 0.451–1.043) in patients with primary resistance (n = 172) and 0.787 (95% CI = 0.606–1.021) in those with secondary resistance (n = 488). In analysis by menopausal status, hazard ratios were 0.689 (95% CI = 0.379–1.252) in premenopausal or perimenopausal women (n = 114) and 0.773 (95% CI = 0.609–0.980) in postmenopausal women (n = 551).

Median time to second disease progression was 23.1 months vs 20.6 months (HR = 0.675, 95% CI = 0.558–0.816), median time to chemotherapy was 50.2 months vs 22.1 months (HR = 0.625,  95% CI = 0.501–0.779), and median chemotherapy-free survival was 25.5 months vs 18.2 months (HR = 0.638, 95% CI = 0.527–0.773).

The investigators reported that no new safety signals were observed relative to the previously reported primary analysis.

The investigators concluded, “Treatment with abemaciclib plus fulvestrant resulted in a statistically significant and clinically meaningful median [overall survival] improvement of 9.4 months for patients with [hormone receptor]-positive, [HER2]-negative [advanced breast cancer] who progressed after prior [endocrine therapy] regardless of menopausal status. Abemaciclib substantially delayed the receipt of subsequent chemotherapy.”

Dr. Sledge, of Stanford University School of Medicine, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by Eli Lilly and Company. For full disclosures of the study authors, visit jamanetwork.com.