Abemaciclib rechallenge after progression on abemaciclib plus endocrine therapy in patients with hormone receptor-positive HER2-negative metastatic breast cancer: results from the phase II again study (WJOG14220B)

In the postMONARCH trial, abemaciclib plus fulvestrant (FUL) yielded a progression-free survival (PFS) of 6.0 months in hormone receptor (HR)-positive HER2-negative metastatic breast cancer patients who progressed after receiving CDK4/6 inhibitor plus endocrine therapy (ET). However, only 8% of these patients had previously received abemaciclib. This multicenter, single-arm, phase II study enrolled patients who developed disease progression after abemaciclib plus ET. Patients were switched from aromatase inhibitor (AI)/tamoxifen (TAM) to FUL or from FUL to AI while continuing abemaciclib. The primary endpoint was PFS. The secondary endpoints were the overall response rate (ORR), clinical benefit rate (CBR), chemotherapy-free interval (CFI), overall survival (OS), and safety. Biomarker analysis was performed based on gene alterations. This study enrolled 65 patients from June 2021 to November 2023; 64 patients could be evaluated following 1 withdrawal. The median PFS for the 64 patients was 4.2 months (90% CI, 2.8-4.4). The median PFS was 7.1 months (95% CI, 3.9-11.3) in patients who switched from abemaciclib plus AI/TAM to abemaciclib plus FUL (n = 28, 43.8%), whereas it was 2.8 months (95% CI, 1.9-4.2) in patients switching from abemaciclib plus FUL to abemaciclib plus AI (n = 36, 56.3%). The ORR was 8.7% (95% CI, 2.4-20.8), the CBR was 23.9% (95% CI, 12.6-38.8), the CFI was 6.7 months (95% CI, 4.9-11.0), and the OS was 28.7 months (95% CI, 25.4-not estimable [NE]). The primary endpoint was not met; switching from abemaciclib plus AI/TAM to abemaciclib plus FUL may be a clinically effective option. JRCTS031210129: Date of registration JUNE 2, 2021.