TY - JOUR
T1 - 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
T2 - an age-specific subgroup analysis of MONARCH 2 and 3 trials
AU - Goetz, Matthew P.
AU - Okera, Meena
AU - Wildiers, Hans
AU - Campone, Mario
AU - Grischke, Eva Maria
AU - Manso, Luis
AU - André, Valérie A.M.
AU - Chouaki, Nadia
AU - San Antonio, Belén
AU - Toi, Masakazu
AU - Sledge, George W.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/4
Y1 - 2021/4
N2 - 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).
AB - 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).
KW - Abemaciclib
KW - Age
KW - Endocrine therapy
KW - HER2−
KW - HR+
KW - Metastatic breast cancer
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U2 - 10.1007/s10549-020-06029-y
DO - 10.1007/s10549-020-06029-y
M3 - Article
C2 - 33392835
AN - SCOPUS:85098710267
SN - 0167-6806
VL - 186
SP - 417
EP - 428
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -