Abstract 272P
Background
TALA is a poly (ADP-ribose) polymerase inhibitor approved in the US, EU, and other countries for the treatment of deleterious/suspected deleterious gBRCA1/2mut HER2-negative ABC. While TALA treatment in the phase 3 EMBRACA trial (NCT01945775) benefited pts regardless of PP, greater improvements in clinical outcomes for TALA vs PCT (capecitabine, eribulin, gemcitabine, or vinorelbine) were seen for pts not treated with PP (PFS hazard ratio [95% CI] 0.76 [0.40–1.45], P = 0.41 for PP vs 0.52 [0.39–0.71], P < 0.0001 for no-PP subgroups). Exploratory analysis revealed that pts with a longer platinum-free interval were more likely to have a longer duration of survival, particularly in the TALA arm. This finding aligns with results from the ABRAZO trial (NCT02034916), which showed greater clinical activity associated with longer platinum-free interval.
Methods
In this post hoc analysis, outcomes were further explored in the PP subgroup of the EMBRACA trial population (data cut-off dates: PFS/ORR 15 Sept 2017; OS/exposure 30 Sept 2019). Previous neoadjuvant/adjuvant (neoadj/adj) platinum therapy was permitted if the pt had a disease-free interval of ≥6 months after the last dose.
Results
Of 431 pts randomized, 76 had PP (46 TALA [22 as neoadj/adj treatment, 22 for advanced disease, 2 for both] and 30 PCT [14 neoadj/adj, 15 advanced, 1 both). Outcomes according to PP setting are shown (Table). Median (range) exposure in the PP subgroup was 6.4 (0.7–38.2) months for TALA (n=46) and 2.1 (0.2–9.2) months for PCT (n=29). Eleven pts (24%) received TALA for ≥12 months, while no pts received PCT for ≥12 months. Table: 272P
Efficacy outcomes by PP setting
| PP in neoadj/adj setting | PP in adv setting | |||
| TALA (n=24) | PCT (n=15) | TALA (n=24) | PCT (n=16) | |
| PFS | ||||
| Events, n | 14 | 9 | 13 | 10 |
| Median (95% CI), mo | 8.9 (4.2–23.2) | 2.9 (1.4–11.3) | 5.6 (1.6–NR) | 4.3 (1.2–27.3) |
| ORRa | ||||
| % (95% CI) | 71.4 (47.8–88.7) | 21.4 (4.7–50.8) | 22.2 (6.4–47.6) | 25.0 (5.5–57.2) |
| OS | ||||
| Events, n | 16 | 10 | 21 | 14 |
| Median (95% CI), mo | 20.9 (9.2–27.9) | 16.8 (3.7–39.9) | 9.6 (6.8–13.6) | 9.4 (4.5–15.6) |
Hazard ratios and odds ratios are not presented due to the small size subgroups, and as these were not prespecified analyses. aIn pts with measurable disease (n=21/18 for TALA; n=14/12 PCT).
Conclusions
Efficacy outcomes generally favored TALA over PCT in the PP subgroup in both early- and late-stage settings but were particularly favorable for pts who received PP as neoadj/adj treatment.
Clinical trial identification
NCT01945775.
Editorial acknowledgement
Editorial assistance 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
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. H.S. Rugo: Financial Interests, Personal, Other, Honoraria: Puma, Samsung and Mylan; Financial Interests, Institutional, Other, Research support: 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. 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, Other, Stock Options: NK Max. 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. 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 stocks/stock options: Pfizer. J. Blum: Financial Interests, Personal, Invited Speaker, 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.