Results from the second interim analysis of MONARCH 3 show that overall survival is numerically longer with abemaciclib plus a non-steroidal aromatase inhibitor (NSAI) versus placebo plus a NSAI in the first-line setting, in post-menopausal patients with HR-positive/HER2-negative advanced breast cancer.
Abemaciclib is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor that—in the MONARCH 2 trial , in combination with fulvestrant—demonstrated significant overall survival (OS) benefit in pre-and post-menopausal patients with HR-positive/HER2-negative advanced breast cancer who had disease progression on prior endocrine therapy. The phase 3 MONARCH 3 trial investigated the efficacy and safety of abemaciclib plus an NSAI in the first-line setting in post-menopausal patients with HR-positive/HER2-negative advanced breast cancer.
Previously, results from MONARCH 3 demonstrated a robust progression-free survival (PFS) benefit (HR, 0.540; P<0.0001) of treatment with abemaciclib/NSAI versus placebo/NSAI, leading to global regulatory approval. Being a gold standard for efficacy, a demonstration of an OS benefit of abemaciclib/NSAI was requested by the European Medicines Agency.
In MONARCH 3, 493 postmenopausal women with HR-positive/HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting were randomized 2:1 to receive abemaciclib/NSAI or placebo/NSAI. Dr. Mathew Goetz (Mayo Clinic) presented the results of the pre-specified second interim OS analysis (data cut-off, July 2, 2021), which was scheduled after approximately 252 events in the intention-to-treat population (80% of planned events for final OS analysis).
With 70.2 months median follow-up, the median OS was 67.1 months for abemaciclib/NSAI versus 54.5 months for placebo/NSAI (HR, 0.754; P=0.0301); this P-value is not statistically significant due to the pre-defined statistical analysis plan. In the subgroup of patients with visceral disease (sVD; n=263), the median OS was 65.1 months versus 48.8 months in the abemaciclib/NSAI and placebo/NSAI arms, respectively (HR, 0.708; P=0.0392); this is, again, not statistically significant due to the statistical analysis plan.
Median chemotherapy-free survival in the intention-to-treat population favored abemaciclib/NSAI over placebo/NSAI (46.7 vs 30.6 months; HR, 0.636). No new safety concerns were observed with prolonged exposure to abemaciclib.
“In the second interim OS analysis from MONARCH 3, a numerically longer OS was observed in both the intention-to-treat and sVD population with the addition of abemaciclib to NSAI,” said Dr. Goetz. “Neither met the threshold for formal statistical significance, but data are maturing favorably.” Follow-up is ongoing for the final OS analysis, which is expected in 2023.
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