Abstract P6-16-01: Health-related quality of life in MONARCH 3: Abemaciclib plus an aromatase inhibitor as initial therapy in women with HR+, HER2- advanced breast cancer
Authors: Goetz MP , Johnston S , Martin M , Tokunaga E , Park IH , Huober J , Toi M , Price GL , Boye M , Li L , Forrester T , Gainford C , Gable J , Carter GC , Sood A , DiLeo A 
Published: May 2019

Abstract
Background: In the MONARCH 3 trial, abemaciclib plus an aromatase inhibitor (AI) significantly improved progression free survival and overall response rate with a generally tolerable safety profile compared to placebo plus AI. Here we report patient-reported outcomes (PRO) including health-related quality of life (Qol), functioning, and symptoms.
Methods: MONARCH 3 was a double-blind, randomized phase III study of abemaciclib or placebo plus an AI in 493 post-menopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer with no prior systemic therapy in the advanced setting. Two European Organization for Research and Treatment of Cancer (EORTC) questionnaires were included: Quality of Life Questionnaire (QLQ)-Core 30 (C30) and the EORTC QLQ-Breast 23 (BR23) that were assessed at baseline, every 2 cycles through cycle 19, then every 3 cycles until treatment discontinuation, and at short-term follow up. Higher scores on functional and health status/QoL outcomes indicate higher/better levels of functioning or health; conversely higher scores on symptom outcomes indicate higher/worse levels of symptom burden. Between-arm comparisons of change from baseline were conducted using mixed model methods. Statistical significance was set at 0.05 and clinical meaningfulness was set at ≥10 points on a 0-100 scale1.
Results: PRO completion rates were &gt;91% through cycle 19; duration of treatment was longer for abemaciclib plus AI patients (median number of cycles 19 vs.15). Compared to the placebo arm, diarrhea PRO scores in the abemaciclib arm showed a clinically (18.68 points) and statistically significant (p&lt;0.001) increase/worsening. By-cycle analysis showed group mean diarrhea scores returned to near-baseline levels post-therapy. Other symptom PROs showed statistically significant (&lt;0.05) but not clinically meaningful differences; fatigue (4.96; p=0.004), systemic therapy side effects (4.48, p&lt;0.001), appetite loss (4.03; p=0.034), and nausea/vomiting (2.77; p=0.013). These results were consistent with the investigator-reported treatment emergent adverse events (TEAEs). Several non-symptom results were also statistically significant but not clinically meaningful including global health/health status (-4.36; p=0.003), role function (-4.25; p=0.025), social function (-3.41, p=0.047), and body image (-5.11, p=0.009). No statistically significant between-treatment differences were observed for physical, emotional, and cognitive functioning or for symptoms of pain, dyspnea, insomnia, constipation, or financial difficulties.
Conclusions: The addition of abemaciclib to an AI resulted in clinically and statistically significant changes in diarrhea without clinically meaningful differences in other symptom scores. Increased GI-related symptoms were consistent with the manageable, reversible AE profile; the highest symptom burden was reported during early visits. No clinically meaningful differences in global health status or functional scores were observed.
ClinicalTrials.gov: NCT02246621
Reference:
1. Osoba D et al. J Clin Oncol 2002;20(14):3106-13.
Citation Format: Goetz MP, Johnston S, Martin M, Tokunaga E, Park IH, Huober J, Toi M, Price GL, Boye M, Li L, Forrester T, Gainford C, Gable J, Carter GC, Sood A, DiLeo A. Health-related quality of life in MONARCH 3: Abemaciclib plus an aromatase inhibitor as initial therapy in women with HR+, HER2- advanced breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-16-01.