Impact of objective response (OR) on patient-reported outcomes (PRO) in patients (pts) with advanced breast cancer (ABC) and a germline BRCA1/2 (gBRCA) mutation in the phase III EMBRACA trial
Authors: P.A. Fasching, R.G.W. Quek, H. Bhattacharyya, S.A. Hurvitz, H.S. Rugo, J. Ettl
Journal: Annals of Oncology (2019)

Background: In EMBRACA, a randomised 2:1 phase 3 open-label study of pts with ABC and a gBRCA mutation, a statistically significant higher OR rate was observed with talazoparib (TALA) (n = 219) vs physician's choice of chemotherapy (PCT; n = 114) (62.6% vs 27.2%; odds ratio, 5.0; 95% CI, 2.9, 8.8; P < 0.001). To evaluate the effects of OR on PRO, we performed post hoc analyses between pts who had OR vs those who did not, based on both treatments combined as well as for each treatment separately. Methods: PRO were assessed on day 1 (baseline), at the start of each treatment cycle (every 3 wks), and at the end of treatment using the EORTC QLQ-C30 and breast cancer module QLQ-BR23. Higher scores indicated better global health status/quality of life (GHS/QoL). Pts were stratified by OR status (with OR vs without OR) within each treatment arm. Repeated measures mixed-effects analyses were performed to compare overall change from baseline scores while controlling for baseline. Time to definitive clinically meaningful deterioration (TDD) (decrease of ≥ 10 points) in GHS/QoL was compared between pts who had OR vs those who did not using stratified log-rank test and Cox proportional hazards model. Results: With the 2 treatment arms combined, an overall change from baseline in GHS/QoL favoured pts with OR vs those without OR (3.9 [95% CI 0.7, 7.1]). Likewise, overall change from baseline favouring pts with OR vs those without OR was also seen in the TALA (2.1 [95% CI -1.6, 5.9]) and PCT arms (3.4 [95% CI -2.2, 9.1]) separately. Additionally, with the 2 treatment arms combined, a greater delay in TTD of GHS/QoL was observed in pts who had an OR vs those without OR (hazard ratio [HR]: 0.67; 95% CI 0.46, 0.98). A delay in TTD in those with OR vs no OR was also seen in the TALA (HR: 0.78; 95% CI 0.49, 1.24) and PCT arms (HR: 0.85; 95% CI 0.43, 1.71) separately. Conclusions: Overall change from baseline and greater delay in TTD in GHS/QoL were observed favouring pts who experienced OR vs those who did not have OR. These results suggest that higher OR rates may lead to better overall improvement from baseline and greater delay in TTD in GHS/QoL in pts with ABC and a gBRCA mutation. Legal entity responsible for the study: Pfizer, Inc. Funding: Pfizer, Inc. Disclosure: P.A. Fasching: Honoraria: Amgen, Novartis, Pfizer, Roche; Consulting or advisory role: Novartis, Pfizer, Roche; Research funding: Amgen, Novartis. R.G.W. Quek: Employee: Pfizer Inc.; Stock ownership: Pfizer Inc., Amgen Inc. H. Bhattacharyya: Employee, own stock: Pfizer. S.A. Hurvitz: Grants: Ambryx, Amgen, Bayer, BI Pharma, Biomarin, Cascadian, Daiichi Sankyo, Dignitana, Genentech, GSK, Lilly, Macrogenics, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Pieris, Puma, Roche, Seattle Genetics; Travel: Lilly, Novartis, OBI Pharma. H.S. Rugo: Research funding to the University of California: Eisai, Genentech, GlaxoSmithKline, Lilly, Macrogenics, Merck, Novartis, OBI Pharma, Pfizer, Plexxikon; Travel expenses: Lilly, Mylan, Puma. J. Ettl: Consulting fees: Lilly, Novartis, Pfizer, Roche, Eisai; Contracted research: Celgene; Honoraria: Pfizer, Roche, Teva, Pierre Fabre; Travel support: Celgene, Novartis, Pfizer.