The cyclin dependent kinase 4/6 inhibitor (CDK4/6i) abemaciclib in combination with endocrine therapy (ET) reduces the risk of recurrence for patients with high-risk early breast cancer and improves progression-free survival (PFS) and overall survival for patients with advanced breast cancer.1-3 The optimal treatment regimen following disease progression on a CDK4/6i-containing regimen remains uncertain. The phase III postMONARCH trial evaluated the efficacy and safety of abemaciclib with a switch in ET after progression on prior CDK4/6i treatment in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer.4
METHODS
The double-blind, randomised phase III postMONARCH study enrolled patients with disease progression on a prior CDK4/6i plus aromatase inhibitor as initial therapy for advanced disease or recurrence on/after adjuvant CDK4/6i + ET. These patients were randomised in a 1:1 ratio to receive abemaciclib plus fulvestrant or placebo plus fulvestrant. The primary endpoint was investigator-assessed progression-free survival (PFS) and secondary endpoints included PFS by blinded independent central review (BICR), objective response rate (ORR), and safety.
RESULTS
Among the 368 randomised patients, median age was 59.0 years and 98.9% received prior CDK4/6i in the advanced setting. Prior CDK4/6i therapy consisted of palbociclib, ribociclib and abemaciclib in 59.0%, 33.2%, and 7.6% of the patients, respectively.
At a median follow-up of 13 months, the addition of abemaciclib to fulvestrant resulted in a 27% reduction in the risk of developing a PFS event. Median PFS was 6.0 vs 5.3 months in the abemaciclib plus fulvestrant vs placebo plus fulvestrant arms, respectively (HR[95% CI]: 0.73[0.57-0.95], nominal p= 0.017). Median PFS assessed by BICR was 12.9 months with abemaciclib plus fulvestrant compared to 5.6 months with placebo plus fulvestrant (HR[95% CI]: 0.55[0.39-0.77], nominal p< 0.001). Among patients with measurable disease, investigator-assessed ORR was higher with abemaciclib plus fulvestrant compared to placebo plus fulvestrant (17% vs 7%, nominal p= 0.015). Overall survival data at this time were immature, with 40 deaths in the abemaciclib plus fulvestrant arm vs. 37 deaths in the placebo plus fulvestrant arm. Grade ≥3 adverse events occurred in 55% and 20% of patients in the abemaciclib plus fulvestrant and placebo plus fulvestrant arms, respectively, with diarrhoea being the most frequently observed adverse event in the abemaciclib plus fulvestrant arm (any grade: 74.6%, grade ≥3: 3.9%). No new safety signals were observed.
CONCLUSIONS
Abemaciclib plus fulvestrant significantly improved PFS after disease progression on a prior CDK4/6i plus ET in patients with HR-positive, HER2-negative advanced breast cancer.
References
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