Editor's Note: PostMONARCH is the first randomized, placebo-controlled phase III study of its kind. At the 2024 ASCO conference, Dr. Kevin Kalinsky from the Winship Cancer Institute of Emory University presented the primary outcomes of the PostMONARCH study, revealing that continued treatment with abemaciclib (Abemaciclib) + fulvestrant benefits patients even after progression on CDK4/6 inhibitor therapy. This article provides a summary of the study's progress for our readers.

Combining CDK4/6 inhibitors with endocrine therapy is the standard first-line treatment option for HR+/HER2- advanced breast cancer (ABC). Although nearly all patients eventually experience disease progression, the optimal treatment strategy for those who have progressed after CDK4/6 inhibitor therapy remains unclear. Real-world studies have shown that abemaciclib can prolong progression-free survival (PFS) in patients who progress after CDK4/6 inhibitor therapy, but the results for other CDK4/6 inhibitors have been inconsistent. The results of the phase III PostMONARCH study, presented at the 2024 ASCO conference, offer new insights into this issue.

The PostMONARCH study is a global, double-blind, placebo-controlled phase III trial designed to evaluate the efficacy of abemaciclib combined with fulvestrant compared to placebo combined with fulvestrant in HR+/HER2- ABC patients who have progressed after CDK4/6 inhibitor + endocrine therapy (ET) treatment. The study included patients who had progressed after CDK4/6 inhibitor + aromatase inhibitor (AI) or CDK4/6 inhibitor + ET therapy, excluding those who had received other prior treatments. The primary endpoint was investigator-assessed PFS, with secondary endpoints including PFS assessed by blinded independent central review (BICR), overall survival (OS), objective response rate (ORR), and safety.

A total of 368 patients were enrolled and randomly assigned to the abemaciclib + fulvestrant group (182 patients) or the placebo + fulvestrant group (186 patients). Almost all patients (99%) were directly enrolled after initial treatment with CDK4/6 inhibitor + ET. The interim analysis showed that abemaciclib + fulvestrant significantly improved investigator-assessed PFS. At the primary analysis, the hazard ratio was 0.73, with the PFS rate in the abemaciclib group being significantly better than that in the placebo group. Subgroup analysis indicated consistent efficacy of abemaciclib across both major clinical and genomic subgroups. Additionally, the ORR in the abemaciclib group was higher than that in the placebo group. BICR-assessed PFS was also improved. OS data is not yet mature, and the safety profile was consistent with the known safety characteristics of abemaciclib.

The PostMONARCH study demonstrates that in HR+/HER2- ABC patients who have progressed after prior CDK4/6 inhibitor therapy, abemaciclib combined with fulvestrant significantly improves PFS compared to placebo combined with fulvestrant, while also exhibiting a favorable safety profile. These results provide a new second-line treatment option for HR+/HER2- ABC patients.