Health-related quality of life (HRQoL) in MONARCH 2: Abemaciclib plus fulvestrant in women with HR+, HER2- advanced breast cancer (ABC) who progressed on 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.

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

“…1). Furthermore, this higher symptom burden of nausea, vomiting, appetite loss, diarrhea, and systemic therapy side effects was more likely to be reported by patients in early visits while on treatment . Dose reductions or omissions and symptom‐specific treatment (i.e., antidiarrheal medication) were effective at reducing these symptoms to baseline or near‐baseline levels at later study visits and at follow‐up for diarrhea .…”

“…Although this study found a higher symptom burden over time in the abemaciclib arm compared with the control arm, as measured in change from baseline for nausea and vomiting, appetite loss, and systemic side effects, these symptoms did not meet the criteria for clinically meaningful differences. Furthermore, for all symptoms, this burden was reported during early study visits and returned to baseline or near‐baseline levels for most patients .…”

Use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in older patients with ER-positive HER2-negative breast cancer: Young International Society of Geriatric Oncology review paper

“…54 Data recently presented from MONARCH-2 using the EORTC QLQ-C30, BR-23, and Brief Pain Inventory short form showed no significant difference in HRQoL between the two treatment groups; however diarrhea, appetite loss, and nausea/vomiting were worse in the abemaciclib arm. 55 These data were not specific to older patients. Further analysis indicated appetite loss and nausea/vomiting were worse with early cycles and returned to near baseline after cycle 7, whereas diarrhea returned to near baseline post-treatment.…”

Are all cyclin-dependent kinases 4/6 inhibitors created equal?

“…In this latter, no significant differences in HRQoL, using the EORTC QLQ-C30, BR-23, and Brief Pain Inventory short form, were observed between the two arms. 56 However, diarrhea, appetite loss, nausea, and vomiting were worse in the abemaciclib group.…”