Abstract 273P
Background
In the EMBRACA trial (NCT01945775), TALA significantly improved progression-free survival (HR=0.54; 95% CI: 0.41–0.71; P < 0.001) and quality of life vs physician’s choice of chemotherapy (PCT) while having a manageable safety profile. The most common adverse events (AEs) with TALA were hematologic (68%) but few resulted in permanent discontinuation (<2%). After accounting for the treatment-emergent periods to normalize for longer exposure due to increased efficacy, the serious AE-associated hospitalization rate was lower for TALA vs PCT. This post hoc analysis explored the clinical characteristics of patient subgroups with hematologic toxicity.
Methods
Baseline characteristics and treatment duration were reported for TALA vs PCT-treated subgroups with hematologic toxicity (G1/2 or G3/4) in the extended follow-up safety population (data cut-off 30 Sept 2019).
Results
The safety population comprised 286 TALA and 126 PCT-treated patients. The most common hematologic AEs with TALA were anemia (G1/2 14.7%; G3/4 40.2%), neutropenia (G1/2 13.6%; G3/4 22.4%), and thrombocytopenia (G1/2 13.6%; G3/4 14.7%); higher rates of neutropenia (G1/2 7.9%; G3/4 34.9%), and lower rates of anemia (G1/2 14.3%; G3/4 4.8%) and thrombocytopenia (G1/2 6.3%; G3/4 1.6%) were seen with PCT. Baseline characteristics for the subgroups with G1/2 or G3/4 anemia are shown (Table). For subgroups with G3/4 anemia, median (range) exposure was 8.1 (0.7–61.4) months (TALA) vs 6.3 (2.1–8.9) months (PCT), and 32 patients (27.8%) (TALA) vs none (PCT) received trial drug for ≥12 months. Table: 273P
Baseline characteristics (safety population)
| Subgroup with G1/2 anemia | Subgroup with G3/4 anemia | |||
| TALA (n=42) | PCT (n=18) | TALA (n=115) | PCT (n=6) | |
| Age, median (range), y | 42.5 (32.0–81.0) | 45.0 (30.0–64.0) | 47.0 (28.0–84.0) | 46.5 (24.0–54.0) |
| <50 y, % | 71 | 61 | 59 | 67 |
| 50–<65 y, % | 14 | 39 | 31 | 33 |
| ≥65 y, % | 14 | 0 | 10 | 0 |
| ECOG PS 0/1/2, % | 52/48/0 | 44/56/0 | 47/50/4 | 67/33/0 |
| Triple-negative, % | 52 | 44 | 47 | 50 |
| HR-positive, % | 48 | 56 | 53 | 50 |
| BRCA1-positive, % | 50 | 44 | 47 | 50 |
| BRCA2-positive, % | 45 | 50 | 49 | 50 |
| Visceral disease, % | 71 | 78 | 68 | 33 |
| Prior cytotoxic regimens for ABC, % | ||||
| 0 | 29 | 28 | 41 | 17 |
| 1 | 50 | 50 | 38 | 50 |
| ≥2 | 21 | 22 | 21 | 33 |
ABC, advanced breast cancer; HR, hormone receptor; PCT, physician’s choice of chemotherapy; TALA, talazoparib.
Conclusions
Baseline characteristics were generally similar between the subgroups with G1/2 and G3/4 anemia treated with TALA; patients with G3/4 anemia tended to be slightly older, have a worse performance status, and be less heavily pretreated.
Clinical trial identification
NCT01945775.
Editorial acknowledgement
Medical writing support was provided by Annette Smith, PhD, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer.
Legal entity responsible for the study
Pfizer.
Funding
Pfizer.
Disclosure
S.A. Hurvitz: Financial Interests, Personal, Other, contracted research support and editorial assistance: Ambrx, Amgen, Arvinas, Bayer, Biomarin, Cascadian Therapeutics, Daiichi Sankyo, Dignitana, Genentech/Roche, Gilead, GSK, Immunomedics, Lilly, MacroGenics, Merrimack, Novartis, Pfizer, Phoenix Molecular Designs, OBI Pharma, Pieris, PUMA, Radius, Sanofi, Sa; Financial Interests, Personal, Other, travel or accommodation expenses: Lilly; Financial Interests, Personal, Stocks/Shares: NK Max. H.S. Rugo: Financial Interests, Personal, Other, Honoraria: Puma, Samsung and Mylan; Financial Interests, Institutional, Other, research support to the University of California San Francisco: Eisai, Roche/Genentech, Eli Lilly, MacroGenics, Merck, Novartis, OBI Pharma, Odonate, Immunomedics, Daiichi Sankyo, Pfizer, Seattle Genetics, Boehringer Ingelheim, Polyphor, AstraZeneca and Sermonix; Financial Interests, Personal, Other, Travel support: AstraZeneca, Daiichi Sankyo, Merck, Mylan, Pfizer, and Novartis. J. Ettl: Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Pierre Fabre, Roche, Tesaro; Financial Interests, Personal, Other, Contracted research: Daiichi Sankyo, Pfizer, Lilly, Novartis, Seattle Genetics, AstraZeneca, Roche, and Odonate; Financial Interests, Personal, Other, Travel support: AstraZeneca, Daiichi Sankyo, Celgene, Pfizer, Novartis, Lilly, and Tesaro. M. Martin: Financial Interests, Personal, Other, Grants: Roche and Novartis; Financial Interests, Personal, Other, Consulting fees: Roche, Novartis, AstraZeneca, GSK, Eli Lilly, Amgen, Taiho, PharmaMar, Puma, and Pfizer. K. Lee: Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Advisory Board: Surface Oncology. A. Goodwin: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Expert Testimony: PBAC committee. T. Usari, S. Lanzalone, C.A. Guenzel: Financial Interests, Personal, Other, Employee and holds stock/stock options: Pfizer. J. Blum: Financial Interests, Personal, Other, Advisor/Consultant: Pfizer, Inc, Amgen, Inc., Biotheranostics, Inc., Novartis, Inc., Genomic Health, Inc., Puma Biotechnology, Inc., Myriad Genetics, Inc., Immunomedics, Inc., Daiichi Sankyo, Inc., Research to Practice, Inc., Athenix, Inc. J.K. Litton: Financial Interests, Institutional, Other, Research support: AstraZeneca, EMD Serono, Genentech, GlaxoSmithKline, Medivation/Pfizer, Novartis, Pfizer, and Zenith Epigenetics; Financial Interests, Personal, Speaker’s Bureau: Clinical Care Options, Med Learning Group, Medpage, Medscape, Physician's Education Resource, and Prime Oncology, and UpToDate; Financial Interests, Personal, Other, honoraria and patent/royalty payments: UpToDate; Financial Interests, Personal, Other, Travel fees: Clinical Care Options, Med Learning Group, Medscape, and Physician's Education Resource; Financial Interests, Personal, Other, Consulting/advisory fees: AstraZeneca, Ayala Pharmaceuticals, Medivation/Pfizer, and Pfizer. All other authors have declared no conflicts of interest.