Abstract P3-11-10: Health-related quality of life (HRQoL) in monarcHER: Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in HR+, HER2+ advanced breast cancer
Authors: Tolaney Sara M , Wardley Andrew M , Zambelli Stefania , Hilton John F. , Troso-Sandoval Tiffany A , Ricci Francesco , Im Seock-Ah , Kim Sung-Bae , Johnston Stephen RD , Chan Arlene , Goel Shom , Catron Kristen , Yang Zhengyu , Gianford M. Corona , Price Gregory L , André Fabrice 
Published: March 2020

Background: Abemaciclib is an oral selective inhibitor of cyclin-dependent kinases 4 and 6 approved for hormone receptor (HR)+, human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer. In the randomized, 3-arm, phase 2 study monarcHER (NCT02675231) for HR+, HER2+ advanced breast cancer (ABC), abemaciclib in combination with trastuzumab (T) and fulvestrant (F) significantly improved investigator-assessed progression-free survival (whereas abemaciclib + T did not) versus (vs) T + physician’s choice of chemotherapy and demonstrated a tolerable safety profile. Here, patient-reported HRQoL, functioning, and symptoms are reported.

Methods: In monarcHER, 237 postmenopausal (surgical, natural, or chemical ovarian suppression) women with ABC and ≥2 prior HER2+ directed therapies in the advanced setting were randomized 1:1:1 to abemaciclib (150 mg PO Q12H every 21 days) + T (IV infusion on D1 every 21 days) with F (500 mg IM on Cycle 1 D1 and D15 and Cycle 2 D8, then Q4W; Arm A) or without F (Arm B) vs T + physician’s choice of chemotherapy (per label every 21 days; Arm C). Supportive measures to manage diarrhea were permitted. Patient-reported outcomes were measured at baseline and at each cycle using the modified Brief Pain Inventory-short form (mBPI-sf) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The EuroQol 5-Dimension 5 Level (EQ-5D 5L) questionnaire was also collected. Higher scores on EORTC QLQ-C30 functional and health status/QoL scales indicate improvement whereas higher scores on EORTC QLQ-C30 symptom scales and mBPI-sf indicate worsening of symptoms/pain. The EQ-5D 5L index score was calculated from a set of item weights to derive a score of 0-1, with 1 representing the best health status. Treatment arm comparisons of change from baseline (all post-baseline visits) were conducted using a mixed model repeated measure, with .05 considered statistically significant. Clinical meaningfulness was defined as a ≥10-point score change from baseline (on a 0-100 scale) for EORTC QLQ-C30 and a 2-point score change from baseline for mBPI-sf.

Results: Patient-reported outcome compliance rates were ≥90% through Cycle 15; the range for median duration of each treatment component of each arm was 7.5-10.0 cycles. Overall, no statistically significant or clinically meaningful changes from baseline differences were observed between treatment arms for mBPI-sf pain scores or EORTC QLQ-C30 global health score, function scales, or for symptoms of fatigue, dyspnea, appetite loss, or financial difficulties. Least square (LS) mean change from baseline differences showed statistically significant improvements in Arm A vs C for EORTC QLQ-C30 symptoms of pain (-6.81; p=.026) and insomnia (-6.39; p=.041). Worsening for the symptom of nausea/vomiting was statistically significant but not clinically meaningful in Arm A vs C (4.08; p=.043). Diarrhea showed a statistically significant and clinically meaningful worsening in Arm A vs C (19.27; p&lt;.001). A by-cycle analysis showed mean nausea/vomiting and diarrhea symptom scores were generally higher during earlier visits and returned to near-baseline levels after treatment discontinuation. The EQ-5D 5L index score improved in Arm A vs C, with an LS mean change from baseline difference of .05 (p=.033).

Conclusions: Quality of life was maintained for patient-reported pain, global health, functioning, and most symptoms when abemaciclib was added to T + F compared with physician’s choice of chemotherapy in patients with HR+, HER2+ ABC. Gastrointestinal-related symptoms were transient and consistent with the manageable, reversible adverse event profile.

Citation Format: Sara M Tolaney, Andrew M Wardley, Stefania Zambelli, John F. Hilton, Tiffany A Troso-Sandoval, Francesco Ricci, Seock-Ah Im, Sung-Bae Kim, Stephen RD Johnston, Arlene Chan, Shom Goel, Kristen Catron, Zhengyu Yang, M. Corona Gianford, Gregory L Price, Fabrice André. Health-related quality of life (HRQoL) in monarcHER: Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in HR+, HER2+ advanced breast cancer [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 P3-11-10.