Dr Kalinsky on the Utility of the postMONARCH Trial Regimen in HR+/HER2– Breast Cancer

Kevin Kalinsky, MD, MS, professor, Department of Hematology and Medical Oncology, director, Division of Medical Oncology, Department of Hematology and Medical Oncology, Emory University School of Medicine; Louisa and Rand Glenn Family Chair in Breast Cancer Research, director, Glenn Family Breast Center, director, Breast Medical Oncology, Winship Cancer Institute of Emory University, discusses the utility of abemaciclib (Verzenio) plus fulvestrant (Faslodex) vs fulvestrant alone in patients with hormone receptor–positive, HER2-negative advanced breast cancer who had disease progression on a CDK4/6 inhibitor and endocrine therapy, according to findings from the phase 3 postMONARCH trial (NCT05169567).

At the 2024 ASCO Annual Meeting, Kalinsky presented findings from the randomized, placebo-controlled study. These findings indicated that the addition of abemaciclib to fulvestrant led to a significant improvement in outcomes such as progression-free survival (PFS) when compared with fulvestrant alone in this patient population. Investigators extensively assessed PFS stratified by key factors, namely the presence of visceral metastasis and prior duration of CDK4/6 inhibition, Kalinsky begins. Approximately three-quarters of patients had been on CDK4/6 inhibitors for at least 12 months, correlating with a hazard ratio (HR) of 0.70 (95% CI, 0.52-0.94) and a resultant median PFS difference of approximately 2 months. Notably, patients without visceral metastasis had a more substantial benefit with the combination than those with visceral metastasis, with a HR of 0.53 (95% CI, 0.34-0.83), translating into an approximately 6-month median PFS advantage, Kalinsky reports.

Regarding specific metastatic sites, such as the liver, the benefit observed was somewhat attenuated compared with that seen in overall visceral metastasis, he expands. This study underscores the viability of this treatment strategy, boasting a well-understood toxicity profile, he adds.

Furthermore, a biomarker analysis revealed that some patients lacked key markers, such as ESR1 mutations or alterations in the PI3K/AKT pathway, according to Kalinsky. For these biomarker-negative patients, this regimen presents a targeted therapeutic option post-CDK4/6 inhibition, he explains. Importantly, irrespective of biomarker status, patients with PI3K/AKT pathway alterations demonstrated consistent benefits in terms of PFS, highlighting the efficacy of this approach in diverse molecular contexts, Kalinsky concludes.