Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials.

Abstract

PURPOSE:

Abemaciclib in combination with endocrine therapy (ET) has demonstrated significant efficacy benefits in HR+ , HER2- advanced breast cancer patients in the Phase 3 studies MONARCH 2 (fulvestrant as ET) and MONARCH 3 (letrozole or anastrozole as ET). Here, we report age-specific safety and efficacy outcomes.

METHODS:

Exploratory analyses of MONARCH 2 and 3 were performed for 3 age groups (<65, 65-74, and ≥75 years). For safety, data were pooled from both studies; for efficacy, a subgroup analysis of PFS was performed for each trial independently.

RESULTS:

Pooled safety data were available for 1152 patients. Clinically relevant diarrhea (Grade 2/3) was higher in older patients receiving abemaciclib + ET (<65, 39.5%; 65-74, 45.2%; ≥75, 55.4%) versus placebo + ET (<65, 6.8%; 65-74, 4.5%; ≥75, 16.0%). Nausea, decreased appetite, and venous thromboembolic events were all moderately higher in older patients. Neutropenia (Grade ≥ 3) did not differ as a function of age in the abemaciclib + ET arm (<65, 25.8%; 65-74, 27.4%; ≥75, 18.1%). Dose adjustments and discontinuation rates were slightly higher in older patients. Abemaciclib + ET improved PFS compared with placebo + ET independent of patient age, with no significant difference in abemaciclib treatment effect between the 3 age groups (MONARCH 2: interaction p-value, 0.695; MONARCH 3: interaction p-value, 0.634). Estimated hazard ratios ranged from 0.523-0.633 (MONARCH 2) and 0.480-0.635 (MONARCH 3).

CONCLUSIONS:

While higher rates of adverse events were reported in older patients, they were manageable with dose adjustments and concomitant medication. Importantly, a consistent efficacy benefit was observed across all age groups.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov: NCT02107703 (first posted April 8, 2014) and NCT02246621 (first posted September 23, 2014).

• Authors: Matthew P Goetz, Meena Okera, Hans Wildiers, Mario Campone, Eva-Maria Grischke, Luis Manso, Valérie A M André, Nadia Chouaki, Belén San Antonio, Masakazu Toi, George W Sledge Jr
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 186 Issue 2 Pg. 417-428 (Apr 2021) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 33392835 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article)

Chemical References

• Aminopyridines
• Benzimidazoles
• Fulvestrant
• abemaciclib
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Age Factors
• Aged
• Aminopyridines
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Benzimidazoles
• Breast Neoplasms (drug therapy)
• Female
• Fulvestrant (therapeutic use)
• Humans
• Receptor, ErbB-2 (genetics)