Pooled Analysis of Post-Progression Treatments after Ribociclib in the MONALEESA-2, -3, and -7 Trials in Patients with HR-Positive/HER2-Negative Advanced Breast Cancer

The MONALEESA studies revealed significant progression-free survival and overall survival (OS) benefits for first-line (1L) ribociclib plus endocrine therapy (ET) in patients with pre-, peri-, and postmenopausal HR-positive/HER2-negative advanced breast cancer. While there is currently no preferred second-line therapy post-progression on a CDK4/6 inhibitor aside from alpelisib in patients harboring PIK3CA mutations, guidelines encourage multiple lines of ET or ET-based treatments before switching to chemotherapy (CT). This pooled, exploratory analysis of the MONALEESA studies examined outcomes of various treatment strategies following progression on ribociclib plus ET.

Data from patients receiving 1L therapy in MONALEESA-2, -3, and -7 were pooled, and patients receiving subsequent therapies after progression were analyzed: those on ET, CT, and targeted therapy. Subsequent CT comprises CT alone or in combination with any other therapy, and targeted therapy includes CDK4/6 inhibitors, mTOR inhibitors, PI3K inhibitors, AKT inhibitors, and others (with or without ET). CT and targeted therapy groups are mutually exclusive. Mean duration of study treatment, first subsequent therapy, and OS were analyzed by Kaplan-Meier methods. Weighted Cox regressions were performed using the inversed propensity scoring matching method to ensure comparable patient characteristics between treatment arms. As only baseline characteristics were used for the estimation of propensity scores, imbalance of prognostic factors at progression may exist, and caution should be taken in interpreting findings.

With a median follow-up time of 74 months, 461 patients treated with ribociclib (81%) and 440 (86%) with placebo discontinued study treatment and received a subsequent therapy. The most common first subsequent therapies in the ribociclib arm were ET monotherapy (40%), CT (29%), and targeted therapy combination (28%); 4% of patients received a different subsequent therapy. For the placebo arms, 34% received CT as a subsequent treatment and 31% each received ET monotherapy or targeted therapy combination; 5% of patients received a different subsequent therapy. In 14% of patients in the ribociclib arm and 20% of patients in the placebo arm, the first subsequent therapy was a CDK4/6 inhibitor; of these, 31% and 12% received ribociclib. Regardless of type of first subsequent therapy, the duration of both the study treatment and the first subsequent therapy was longer for patients treated with ribociclib versus placebo. In both arms of the study, patients receiving subsequent CT had the shortest duration on study treatment; those on subsequent targeted therapy combination had the longest duration on study treatment. Among patients on 1L ribociclib plus ET, after matching for baseline characteristics, subsequent CDK4/6 inhibitor use was associated with the longest median OS at 84 months, followed by ET monotherapy at 60 months, non-CDK4/6 inhibitor targeted therapy at 52 months, and CT at 37 months.

This large, pooled analysis of the MONALEESA studies shows that duration of any subsequent therapy was longer post-1L ribociclib plus ET versus placebo plus ET, with subsequent CT being utilized less frequently for patients on ribociclib versus placebo. These outcomes with subsequent therapies following 1L ribociclib suggest a posttreatment effect that should be further explored.

Source:

Hamilton E, Spring L, Fasching PA, et al. Pooled analysis of post-progression treatments after first-line ribociclib + endocrine therapy in patients with HR+/HER2- advanced breast cancer in the MONALEESA-2, -3, and -7 studies. San Antonio Breast Cancer Symposium 2022. Abstract P4-01-42.