Abstract PD10-01: Patient-reported outcomes in patients with HER2- advanced breast cancer and a germline BRCA1/2 mutation receiving talazoparib vs physician’s choice of chemotherapy: A focus on EMBRACA ECOG performance status subgroups
Authors: Rugo Hope S , Quek Ruben G. W. , Bhattacharyya Helen , Gonçalves Anthony , Ettl Johannes , Hurvitz Sara A. 
Published: March 2020

Abstract
Background EMBRACA was a randomized 2:1 open-label Phase 3 study (NCT01945775). As part of key subgroup analyses of EMBRACA, significant improvements in progression-free survival with talazoparib (TALA) vs physician’s choice of chemotherapy (PCT) were observed in HER2- germline BRCA1/2 mutated (gBRCA1/2mut) advanced breast cancer (ABC) in patient (pt) subgroups with an Eastern Cooperative Oncology Group (ECOG) performance status of grade 0 and grade &gt;0. These post hoc analyses evaluated pt-reported outcomes (PROs) in both ECOG subgroups. Methods PRO was assessed at baseline (Day 1), start of each treatment cycle (every 3 weeks), and end of treatment, using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and breast cancer module QLQ-BR23. Higher scores in global health status (GHS)/quality of life (QoL) and functional scales indicate better GHS/QoL and functioning, respectively; higher scores in symptom scales indicate worse symptom severity. PRO analyses, performed separately in ECOG performance status grade 0 and &gt;0 subgroups, for GHS/QoL, functional, and symptom scales include overall mean change from baseline (per longitudinal repeated measures mixed-effects model) and time to definitive clinically meaningful deterioration (TTD; per survival analysis methods). Between-arm comparisons of TTD were made using stratified log-rank test and Cox proportional hazards model. Results Baseline scores were similar between arms. A statistically significant estimated overall change from baseline in GHS/QoL favored TALA vs PCT for both ECOG performance status grade 0 (8.1 [95%CI: (3.3, 13.0)] P&lt;0.001) and grade &gt;0 (9.4 [95%CI: (2.8, 16.0)] P=0.005) subgroups. A statistically significant estimated overall change from baseline in pt-reported pain symptoms favored TALA vs PCT for both ECOG performance status grade 0 (-13.3 [95%CI: -18.9, -7.8]; P&lt;0.001) and grade &gt;0 (-16.4 [95%CI: -25.3, -7.5]; P&lt;0.001) subgroups. A statistically significant estimated overall change from baseline in pt-reported fatigue favored TALA vs PCT for both ECOG performance status grade 0 (-9.5 [95%CI: -15.4, -3.6]; P=0.002) and grade &gt;0 (-19.4 [95%CI: -28.8, -10.1]; P&lt;0.001) subgroups. A statistically significant delay in TTD favoring TALA was observed in GHS/QoL for both ECOG performance status grade 0 (median: 24.3 vs 10.3 mos, HR=0.40 [95%CI: 0.24, 0.67]; P&lt;0.001) and grade &gt;0 (median: 21.1 vs 6.0 mos, HR=0.34 [95%CI: 0.19, 0.61]; P&lt;0.001) subgroups. A statistically significant delay in TTD favoring TALA was observed in pt-reported pain symptoms for both ECOG performance status grade 0 (median: 21.5 vs 5.9 mos, HR=0.29 [95%CI: 0.17, 0.49]; P&lt;0.001) and grade &gt;0 (median: not reached vs 7.5 mos, HR=0.36 [95%CI: 0.19, 0.68]; P=0.001) subgroups. A statistically significant delay in TTD favoring TALA was observed in pt-reported fatigue for both ECOG performance status grade 0 (median: 17.1 vs 6.1 mos, HR=0.40 [95%CI: 0.25, 0.65]; P&lt;0.001) and grade &gt;0 (median: 16.9 vs 7.1 mos, HR=0.41 [95%CI: 0.24, 0.69]; P&lt;0.001) subgroups. When comparing between arms, none of the analyses in either the ECOG performance status grade 0 or &gt;0 subgroup yielded statistically significant PRO results favoring PCT. Conclusions In pts with HER2- ABC, TALA (vs PCT) resulted in significantly better change from baseline and significantly delayed TTD in GHS/QoL, pt-reported pain symptoms and fatigue in both ECOG performance status grade 0 and &gt;0 subgroups; none of the analyses significantly favored PCT. These results further support the positive risk-benefit profile of TALA vs PCT in pts with HER2- gBRCA1/2mut ABC in both ECOG performance status subgroups of grade 0 and &gt;0. Funding: Pfizer Inc.
Citation Format: Hope S Rugo, Ruben G. W. Quek, Helen Bhattacharyya, Anthony Gonçalves, Johannes Ettl, Sara A. Hurvitz. Patient-reported outcomes in patients with HER2- advanced breast cancer and a germline BRCA1/2 mutation receiving talazoparib vs physician’s choice of chemotherapy: A focus on EMBRACA ECOG performance status subgroups [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 PD10-01.