Health-Related Quality of Life in MONARCH 3: Abemaciclib plus an Aromatase Inhibitor as Initial Therapy in HR+, HER2- Advanced Breast Cancer

Abstract

Background: MONARCH 3, a phase III trial (NCT02246621) of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), previously demonstrated significantly improved progression-free survival in patients receiving abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI). This study evaluated patient-reported outcomes, including global health-related quality of life (HRQoL), functioning, and symptoms.

Methods: Patients were randomly assigned 2:1 to receive abemaciclib (150 mg twice daily; n = 328) or placebo (n = 165), plus 1 mg anastrozole or 2.5 mg letrozole daily. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Breast Cancer-Specific Quality of Life Questionnaire HRQoL instruments were administered at baseline, every two cycles during cycles 2 through 19 (each cycle being 28 days), every three cycles thereafter, and once at a short-term posttherapy follow-up visit (approximately 30 days after discontinuation). Longitudinal mixed regression and Cox proportional hazards models evaluated postbaseline change and time to sustained deterioration (TTSD), respectively.

Results: Baseline scores were similar between treatment arms. Although select scores statistically favored the placebo arm, global HRQoL, most symptoms, and functioning scales did not meet the threshold for clinically meaningful differences between treatment arms. Only diarrhea favored the placebo arm with statistically and clinically meaningful differences. There were no TTSD differences between treatment arms for global HRQoL, most symptoms (except diarrhea), or functioning.

Conclusion: Over a 2-year period, there were no clinically meaningful differences in global HRQoL, functioning, and most symptoms for patients receiving abemaciclib plus NSAI compared with NSAI alone. Only diarrhea favored the placebo arm, consistent with prior safety data, which has been shown to be manageable and reversible. Combined with clinical efficacy, results support treatment with abemaciclib plus NSAI for postmenopausal women with HR+, HER2- ABC.

Implications for practice: The addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) was not associated with a clinically meaningful detriment in patient-reported global health-related quality of life, functioning, and most symptoms in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Prior studies have also demonstrated clinical efficacy of abemaciclib plus NSAI compared with NSAI alone, including improved progression-free survival and objective response rate. These results also complement previously reported toxicity data, as measured by investigator-assessed adverse events. Taken together, these results support treatment with abemaciclib plus NSAI for postmenopausal women with HR+, HER2- ABC.

Keywords: Abemaciclib; Advanced breast cancer; Cyclin-dependent kinase 4/6 inhibitor; Health-related quality of life; Patient-reported outcomes.

Figure 1

CONSORT diagram. *, One patient who was randomly assigned to the placebo arm actually received abemaciclib during cycle 1. This patient is counted in the abemaciclib safety population. Abbreviation: NSAI, nonsteroidal aromatase inhibitor.

Figure 2

Forest plot of mean differences, obtained with longitudinal mixed regression models, between study arms in change from baseline scores for the European Organization for Research and Treatment of Cancer Quality of Life Core 30. Higher scores on symptoms indicated greater symptom burden or worsening, and higher scores for global health status and functioning items indicated better function or improvement. Given this discrepancy, the sign for scores for the global health status and functioning items were reversed for this figure to be consistent with the symptom scores. Abbreviations: CI, confidence interval; NSAI, nonsteroidal aromatase inhibitor.

Figure 3

Forest plot of mean differences, obtained with longitudinal mixed regression models, between study arms in change from baseline scores for the Breast Cancer Questionnaire. Higher scores on symptoms indicated greater symptom burden or worsening, and higher scores for functioning items indicated better function or improvement. Given this discrepancy, the sign for scores of functioning items were reversed for this figure to be consistent with the symptom scores. Abbreviations: CI, confidence interval; NSAI, nonsteroidal aromatase inhibitor.

Figure 4

Patient‐reported diarrhea, as measured by the European Organization for Research and Treatment of Cancer, by cycle among patients taking abemaciclib plus a nonsteroidal aromatase inhibitor.

Figure 5

Forest plot of time to sustained deterioration of European Organization for Research and Treatment of Cancer Quality of Life Core 30 global health, symptoms, and functioning items. Abbreviations: CI, confidence interval; HR, hazard ratio; NSAI, nonsteroidal aromatase inhibitor.

Figure 6

Forest plot of time to sustained deterioration of the Breast Cancer Questionnaire symptoms and functioning items. Abbreviations: CI, confidence interval; HR, hazard ratio; NSAI, nonsteroidal aromatase inhibitor.