Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician's Choice Standard-of-Care Chemotherapy

Hope S Rugo; Johannes Ettl; Sara A Hurvitz; Anthony Gonçalves; Kyung-Hun Lee; Louis Fehrenbacher; Lida A Mina; Sami Diab; Natasha E Woodward; Rinat Yerushalmi; Annabel Goodwin; Joanne L Blum; Miguel Martin; Ruben G W Quek; Iulia Cristina Tudor; Helen Bhattacharyya; Eric Gauthier; Jennifer K Litton; Wolfgang Eiermann

doi:10.1093/jncics/pkz085

Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician's Choice Standard-of-Care Chemotherapy

JNCI Cancer Spectr. 2019 Oct 21;4(1):pkz085. doi: 10.1093/jncics/pkz085. eCollection 2020 Feb.

Authors

Hope S Rugo¹, Johannes Ettl², Sara A Hurvitz³, Anthony Gonçalves⁴, Kyung-Hun Lee⁵, Louis Fehrenbacher⁶, Lida A Mina⁷, Sami Diab⁸, Natasha E Woodward⁹, Rinat Yerushalmi¹⁰, Annabel Goodwin¹¹, Joanne L Blum¹², Miguel Martin¹³, Ruben G W Quek¹⁴, Iulia Cristina Tudor¹⁵, Helen Bhattacharyya¹⁶, Eric Gauthier¹⁴, Jennifer K Litton¹⁷, Wolfgang Eiermann¹⁸

Affiliations

¹ University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
² Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
³ University of California, Los Angeles/Jonsson, Jonsson Comprehensive Cancer Center (UCLA/JCCC), Los Angeles, CA.
⁴ Institut Paoli-Calmettes, Marseille, France.
⁵ Seoul National University Hospital, Seoul, South Korea.
⁶ Kaiser Permanente, Northern California, Vallejo, CA.
⁷ MD Anderson Cancer Center, Gilbert, AZ.
⁸ Rocky Mountain Cancer Centers, Littleton, CO.
⁹ Mater Cancer Care Centre-Mater Health Services/Mater Research Institute, University of Queensland, South Brisbane, Queensland, Australia.
¹⁰ Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
¹¹ Concord Repatriation General Hospital, Concord, New South Wales, Australia.
¹² Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX.
¹³ Instituto de Investigación Sanitaria Gregorio Marañón, CIBERONC, GEICAM, Universidad Complutense, Madrid, Spain.
¹⁴ Pfizer Inc., San Francisco, CA.
¹⁵ Former employee of Pfizer Inc.
¹⁶ Pfizer Inc., New York, NY.
¹⁷ The University of Texas MD Anderson Cancer Center, Houston, TX.
¹⁸ Interdisziplinäres Onkologisches Zentrum München, Munich, Germany.

Abstract

Background: Talazoparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that causes death in cells with breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations.

Methods: EMBRACA (NCT01945775) was a randomized phase III study comparing efficacy, safety, and patient-reported outcomes (PROs) of talazoparib (1 mg) with physician's choice of chemotherapy (PCT: capecitabine, eribulin, gemcitabine, vinorelbine) in locally advanced or metastatic breast cancer with a germline BRCA1/2 (gBRCA1/2) mutation. Prespecified patient subgroups were analyzed for progression-free survival, objective response, clinical benefit, duration of response, and safety. PROs were evaluated in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) or triple-negative breast cancer (TNBC) subgroups.

Results: Of 431 patients, 287 were randomly assigned to talazoparib and 144 to PCT. Prespecified subgroup analyses showed prolonged progression-free survival with talazoparib (HR+/HER2-: hazard ratio = 0.47, 95% confidence interval = 0.32 to 0.71; TNBC: hazard ratio = 0.60, 95% confidence interval = 0.41 to 0.87) and greater objective response rate (odds ratio = 1.97 to 11.89), clinical benefit rate (odds ratio = 2.05 to 7.77), and duration of response with talazoparib in all subgroups. PROs in HR+/HER2- and TNBC subgroups showed consistent overall improvement and delay in time to definitive clinically meaningful deterioration with talazoparib vs PCT. Across subgroups, common adverse events included anemia, fatigue, and nausea with talazoparib and neutropenia, fatigue, and nausea with PCT. Seven patients (2.4%) receiving talazoparib had grade II alopecia and 22.7% had grade I alopecia.

Conclusions: Across all patient subgroups with gBRCA-mutated advanced breast cancer, talazoparib demonstrated clinically significant superiority in outcomes compared with PCT.