Abstract P1-19-10: Safety and efficacy of abemaciclib plus endocrine therapy (ET) in elderly patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+, HER2-) advanced breast cancer: An age-specific subgroup analysis of MONARCH 2 and 3 trials
Authors: Goetz Matthew P. , Okera Meena , Wildiers Hans , Campone Mario , Grischke Eva-Maria , Manso Luis , Andre Valerie Anne Marie , Chong Amy Lee , Antonio Belen San , Toi Masakazu , Sledge George W 
Published: March 2020

Abstract
Background: Breast cancer incidence and mortality rates are increased in patients’ older than 65 years. However, there are limited reports on age-specific efficacy, safety, and drug tolerability, particularly in elderly patients older than 75 years old. Abemaciclib demonstrated clinically meaningful progression-free survival (PFS) improvement in combination with endocrine therapy (ET) in HR+, HER2- advanced breast cancer patients in the Phase 3 studies, MONARCH 2 and 3. Here we report exploratory subgroup analyses of MONARCH 2 and 3 to provide age-specific outcomes.
Methods: In MONARCH 2 (NCT02107703), patients progressing while on prior ET received abemaciclib (or placebo) plus fulvestrant; in MONARCH 3 (NCT02246621), postmenopausal women with no prior systemic therapy for recurrent or metastatic breast cancer received abemaciclib (or placebo) plus letrozole or anastrozole. Exploratory outcome analyses of MONARCH 2 and 3 studies were performed for three age groups (women aged &lt;65, 65-74, and ≥75 years). Using pooled safety data, we performed age-specific subgroup analyses of the most common treatment-emergent adverse events (TEAEs) associated with either ET or ET plus abemaciclib. To assess the impact of age on efficacy, a subgroup analysis of PFS was performed using a Cox model for each trial independently.
Results: Pooled safety data were available for 1152 patients treated in MONARCH 2 and 3 trials, including 59.7% pts &lt;65 years, 28.7% pts between 65 and 74 years, and 11.5% pts ≥ 75 years. Of those, 768 women received abemaciclib plus ET and 384 women received placebo plus ET. The most frequent TEAE was diarrhea and the most common Grade ≥3 TEAE was neutropenia. While diarrhea (any grade) occurred with similar incidence in abemaciclib-treated patients across age groups, clinically relevant diarrhea (Grade 2/3) was higher in the elderly (&lt;65, 39.5%; 65-74, 45.2%; ≥75, 55.4%); however, in the ≥75 group, diarrhea (Grade 2/3) incidence was also higher for placebo plus ET (&lt;65, 6.8%; 65-74, 4.5%; ≥75, 16.0%). Similarly, nausea and decreased appetite were moderately higher (by 10-20%) in the 2 abemaciclib-treated elderly subgroups. Fatigue (any grade) was higher in the 2 abemaciclib-treated elderly subgroups (&lt;65, 34.8%; 65-74, 48.4%; ≥75, 51.8%), while no differences were found across the 3 placebo subgroups. In contrast, the rates of Grade 3/4 neutropenia did not differ as a function of age in either the abemaciclib plus ET arm (&lt;65, 25.8%; 65-74, 27.4%; ≥75, 18.1%) or placebo plus ET arm. For efficacy, a consistent PFS benefit was observed with abemaciclib plus ET versus placebo plus ET across all three age-specified subgroups in both studies (Table).
Conclusion: Abemaciclib in combination with ET demonstrates a tolerable safety profile and consistent efficacy benefit across all age subgroups examined, supporting the use of this combination in elderly patient populations. Despite the limited number of patients in the ≥75 group with potentially confounding comorbidities, the safety data suggest that patient education and appropriate management of toxicities, including dose adjustments and use of supportive medication for gastrointestinal toxicities, could maximize the benefit of abemaciclib.
Table: Age-specified PFS outcomes from MONARCH 2 and 3MONARCH 2MONARCH 3Age GroupAbemaciclib + ETPlacebo + ETHR (95% CI)P-value *Abemaciclib + ETPlacebo + ETHR (95% CI)P-value *Events/NEvents/NEvents/NEvents/N&lt;65140/29192/1330.52 (0.40, 0.68)0.69581/18065/910.48 (0.35, 0.67)0.63465-7461/11442/600.63 (0.43, 0.94)40/10631/540.64 (0.40, 1.02)≥7521/4123/300.62 (0.34, 1.11)17/4212/200.54 (0.26, 1.13)Abbreviations: CI, confidence interval; ET, endocrine therapy; HR, hazard ratio; PFS, progression-free survival.*P-value corresponds to the interaction test between age and treatment.
Citation Format: Matthew P. Goetz, Meena Okera, Hans Wildiers, Mario Campone, Eva-Maria Grischke, Luis Manso, Valerie Anne Marie Andre, Amy Lee Chong, Belen San Antonio, Masakazu Toi, George W Sledge Jr. Safety and efficacy of abemaciclib plus endocrine therapy (ET) in elderly patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+, HER2-) advanced breast cancer: An age-specific subgroup analysis of MONARCH 2 and 3 trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-10.