Health-Related Quality of Life in MONARCH 2: Abemaciclib plus Fulvestrant in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer After Endocrine Therapy

Abstract

Background: In the phase III MONARCH 2 study (NCT02107703), abemaciclib plus fulvestrant significantly improved progression-free survival (PFS) versus placebo plus fulvestrant in patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer (ABC). This study assessed patient-reported pain, global health-related quality of life (HRQoL), functioning, and symptoms.

Materials and methods: Abemaciclib or placebo (150 p.o. mg twice daily) plus fulvestrant (500 mg, per label) were randomly assigned (2:1). The modified Brief Pain Inventory, Short Form (mBPI-sf); European Organization for Research and Treatment of Cancer (EORTC) QoL Core 30 (QLQ-C30); and Breast Cancer Questionnaire (QLQ-BR23) assessed outcomes. Data were collected at baseline, cycle 2, every two cycles 3-13, thereafter at every three cycles, and 30 days postdiscontinuation. Longitudinal mixed regression and Cox proportional hazards models assessed postbaseline change and time to sustained deterioration (TTSD) by study arm.

Results: On-treatment HRQoL scores were consistently maintained from baseline and similar between arms. Patients in the abemaciclib arm (n = 446) experienced a 4.9-month delay in pain deterioration (mBPI-sf), compared with the control arm (n = 223), and significantly greater TTSD on the mBPI-sf and analgesic use (hazard ratio, 0.76; 95% CI, 0.59-0.98) and QLQ-C30 pain item (hazard ratio, 0.62; 95% CI, 0.48-0.79). TTSD for functioning and most symptoms significantly favored the abemaciclib arm, including fatigue, nausea and vomiting, and cognitive and social functioning. Only diarrhea significantly favored the control arm (hazard ratio, 1.60; 95% CI, 1.20-2.10).

Conclusion: HRQoL was maintained on abemaciclib plus fulvestrant. Alongside superior PFS and manageable safety profile, results support treatment with abemaciclib plus fulvestrant in a population of patients with endocrine-resistant HR+, HER2-negative ABC.

Implications for practice: In MONARCH 2, abemaciclib plus fulvestrant demonstrated superior efficacy and a manageable safety profile for patients with in hormone receptor-positive (HR+), HER2-negative (-) advanced breast cancer (ABC). Impact on health-related quality of life (HRQoL) is important to consider, given the palliative nature of ABC treatment. In this study, abemaciclib plus fulvestrant, compared with placebo plus fulvestrant, significantly delayed sustained deterioration of pain and other patient-reported symptoms (including fatigue, nausea, vomiting), and social and cognitive functioning. Combined with demonstrated clinical benefit and tolerability, the stabilization of patient-reported symptoms and HRQoL further supports abemaciclib plus fulvestrant as a desirable treatment option in endocrine resistant, HR+, HER2- ABC.

Keywords: Abemaciclib; Advanced breast cancer; Patient-reported outcomes; Quality of life.

Figure 1

CONSORT diagram.

Figure 2

Time to deterioration of modified Brief Pain Inventory, Short Form “worst pain” and increased analgesic use.Abbreviations: CI, confidence interval; HR, hazard ratio.

Figure 3

Forest plot of time to sustained deterioration for pain, as measured by the modified Brief Pain Inventory, Short Form (mBPI‐sf) with analgesic use, mBPI‐sf alone, and the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ‐C30).Abbreviations: CI, confidence interval; HR, hazard ratio.

Figure 4

Forest plot of time to sustained deterioration of European Organization for Research and Treatment of Cancer Quality of Life Core 30 symptom and functioning items.Abbreviations: CI, confidence interval; HR, hazard ratio.

Figure 5

Forest plot of time to sustained deterioration of the European Organization for Research and Treatment of Cancer Breast Cancer Questionnaire symptom and functioning items.Abbreviations: CI, confidence interval; HR, hazard ratio.