Benefit of abemaciclib plus fulvestrant after progression on a CDK4/6 inhibitor

The addition of abemaciclib to fulvestrant led to a significant improvement in progression-free survival (PFS) compared with fulvestrant alone in patients with advanced HR-positive/HER2-negative breast cancer who had disease progression on a CDK4/6 inhibitor plus endocrine therapy, according to data from the phase 3 postMONARCH study.

The combination of a CDK4/6 inhibitor plus endocrine therapy is a first-line treatment option for patients with advanced, HR-positive/HER2-negative breast cancer. Although disease progression occurs in nearly all patients, the optimal treatment for patients who experience progression on a CDK4/6 inhibitor plus endocrine therapy remains uncertain.

The phase 3 postMONARCH trial (NCT05169567) explored the efficacy of fulvestrant plus abemaciclib versus placebo in patients with advanced, HR-positive/HER2-negative breast cancer who progressed on first-line treatment with a CDK4/6 inhibitor plus endocrine therapy. Prof. Kevin Kalinsky (Emory School of Medicine, GA, USA) presented the results [1].

In postMONARCH, 368 participants who showed disease progression on first-line therapy with (any) CDK4/6 inhibitor plus endocrine therapy were 1:1 randomised to treatment with abemaciclib plus fulvestrant or placebo plus fulvestrant. The primary endpoint was investigator-assessed PFS, and the secondary endpoints included PFS assessed via blinded independent central review (BICR).

The primary analysis showed a significantly improved median PFS in participants treated with abemaciclib plus fulvestrant versus fulvestrant alone: 6.0 versus 5.3 months (HR 0.73; 95% CI 0.57–0.95; P=0.02). In other words, the addition of abemaciclib led to a 27% reduction in the risk of developing a PFS event. In particular, abemaciclib was beneficial in participants without visceral metastases (HR 0.53; 95% CI 0.34–0.8).

Data from the secondary analysis also showed that PFS was improved by abemaciclib compared with placebo when assessed by BICR. The median PFS with abemaciclib/fulvestrant was 12.9 months, versus 5.6 months with fulvestrant alone (HR 0.55; 95% CI 0.39–0.77; P=0.0004). In other words, the addition of abemaciclib led to a 45% reduction in the risk of developing a PFS event. The 6-month PFS rates in the abemaciclib and placebo arms were 68% and 45%, respectively. The safety data observed in this study were consistent with that previously reported for abemaciclib.

“Abemaciclib plus fulvestrant offers a targeted therapy option after disease progression on a CDK4/6 inhibitor for patients with HR-positive/HER2-negative advanced breast cancer,” concluded Prof. Kalinsky.

1. Kalinsky K, et al. Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on prior CDK4/6 inhibitor plus endocrine therapy: primary outcome of the phase 3 postMONARCH trial. Abstract LBA1001, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

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Posted on 18 July 202418 July 2024