Efficacy of talazoparib and enzalutamide in mCRPC patients previously treated with androgen receptor pathway inhibitors (ARPI) or docetaxel: Post hoc analysis from both cohorts in TALAPRO-2 study

BackgroundTALAPRO-2 (NCT03395197) is a Phase 3 trial of talazoparib (TALA) + enzalutamide (ENZA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). We conducted a post hoc analysis of radiographic progression free survival (rPFS) by prior androgen receptor pathway inhibitors (ARPI; abiraterone or orteronel) or by prior docetaxel.MethodsTime-to-event was summarized using the Kaplan-Meier method and compared between treatment arms using a stratified log-rank test except for the subgroup analysis of rPFS by prior ARPI/docetaxel which used an unstratified model due to small patient numbers in some of the subgroups. All reported P values are two-sided.ResultsIn the all-comers cohort, 23 pts treated with TALA+ENZA received prior ARPI and 86 pts received docetaxel, compared to 27 and 93 pts respectively in the placebo (PBO)+ENZA arm. Median rPFS for the pts previously treated by ARPI was 11.0 months (5.6, 16.4) in the TALA+ENZA arm and 1.9 months (1.8, 11.0) in the PBO+ENZA arm with a hazard ratio (HR) of 0.566 (0.277, 1.157; p=0.11). For the pts previously treated with docetaxel, median rPFS was not estimable (NE) (NE, NE) in TALA+ENZA arm and 19.3 months (11.7, 25) in PBO+ENZA arm, with an HR of 0.508 (0.321, 0.805; p=0.0034) in the all-comers population. In the HRR deficient cohort, 17 pts treated with TALA+ENZA received prior ARPI, and 57 pts received docetaxel, compared to 17 and 60 pts respectively in the PBO+ENZA arm. Median rPFS for the pts previously treated by ARPI was 13.7 months (8.4, NE) in the TALA+ENZA arm and 5.6 months (1.9, NE) in the PBO+ENZA arm with an HR of 0.528 (0.196, 1.420; p=0.19). For patients previously treated with docetaxel, median rPFS was NE (16.4, NE) for TALA+ENZA arm and 11.0 months (9.2, 16.4) for the PBO+ENZA arm with an HR of 0.386 (0.217, 0.689; p=0.00048).ConclusionsAlthough numbers in ARPI or docetaxel pretreated cohorts are small, this post hoc subgroup analysis shows the same improved trend in rPFS benefit by TALA+ENZA in both cohorts of the TALAPRO-2 study.Clinical trial identificationNCT03395197.Legal entity responsible for the studyPfizer is responsible for the governance, coordination, and running of the study.FundingThis study was funded by Pfizer Inc. Astellas Pharma Inc. provided enzalutamide.DisclosureN. Agarwal: Financial Interests, Personal, Invited Speaker, Invited speaker: Medscape; Financial Interests, Personal, Invited Speaker, Invited Speaker: Onclive, Research to Practice, Clinical Care Options; Financial Interests, Institutional, Other, I serve in the leadership of my cancer center (Huntsman Cancer Institute, University of Utah. Salt Lake City, UT, USA). There are multiple research projects sponsored by these companies which pay money to my institution: Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, CRISPR, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GSK, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, Telix, Tracon; Financial Interests, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharmas with no personal honorarium.: AstraZeneca, Calithera, CRISPR, Eli Lilly, Exelixis, Immunomedics, Merck, Pfizer,; Financial Interests, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharma companies with no personal honorarium.: Merck, Nektar, New Link Genetics, Oric, Pfizer, Prometheus, Rexahn, Takeda, Telix,Tracon; Financial Interests, Trial Chair, One of the two co-chairs of the clinical trials sponsored by these pharma companies. I have not received any honorarium for these roles.: Pfizer, Exelixis, Janssen, Telix.; Non-Financial Interests, Member, I am a long-standing member of ASCO and a volunteer. I was awarded the fellow of ASCO in 2023. I also act as the editor of the ASCO Daily News as a volunteer: Amercian Society of Clinical Oncology; Non-Financial Interests, Member, I am a member of this NCI and NCTN-sponsored cooperative clinical trial network group: SWOG; Non-Financial Interests, Member, I am a member of these professional organizations: AACR, AUA, PCF. A.A. Azad: Financial Interests, Personal, Advisory Board: Astellas, Novartis, Sanofi, AstraZeneca, Tolmar, Telix, Merck Serono, Janssen, Bristol Myers Squibb, Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Merck Sharpe Dohme, Daiichi Sankyo, Arvinas; Financial Interests, Personal, Other, Consultant: Aculeus Therapeutics; Financial Interests, Personal, Invited Speaker: Astellas, Janssen, Novartis, Amgen, Ipsen, Bristol Myers Squibb, Merck Serono, Bayer; Financial Interests, Personal, Other, Travel + Accommodation: Astellas, Merck Serono, Amgen, Novartis, Janssen, Tolmar, Pfizer, Bayer; Financial Interests, Personal, Research Grant: Astellas, Merck Serono, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Astellas, Pfizer, Exelixis; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Aptevo Therapeutics, AstraZeneca, GSK, Pfizer, Astellas, SYNthorx, Bionomics, Sanofi, Ipsen, Exelixis, Merck Sharpe Dohme, Janssen, Eli Lilly, Gilead Sciences, Merck Serono, Hinova; Financial Interests, Institutional, Trial Chair: Bayer; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Hinova; Financial Interests, Personal, Trial Chair: Janssen, AstraZeneca; Non-Financial Interests, Leadership Role, Chair, Translational Research Committee: ANZUP Cancer Trials Group; Non-Financial Interests, Leadership Role, Member, Scientific Advisory Committee: ANZUP Cancer Trials Group; Non-Financial Interests, Leadership Role, Chair, Urologic Oncology Committee: Clinical Oncology Society of Australia; Non-Financial Interests, Other, Editorial Board Member: BMC Urology; Non-Financial Interests, Other, Associate Editor: Cancer Research Communications, Frontiers in Oncology. J.C. Galceran: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Ipsen, Johnson & Johnson, MSD Oncology, Novartis, Pfizer, Roche, Sanofi, Bayer; Financial Interests, Institutional, Funding: AB Science, Aragon Pharmaceuticals, Inc., Arog Pharmaceuticals, Astellas Pharma, AstraZeneca AB, Aveo Pharmaceuticals, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics, Boehringer Ingelheim Espana, S.A., Bristol Myers Squibb International (BMS), Clovis Oncology, Inc., Cougar Biotechnology Inc., Deciphera Pharmaceuticals LLC, Exelixis, Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK, Incyte Corporation, Janssen-Cilag International NV, Karyopharm Therapeutics, Inc., Laboratories Leurquin Mediolanum SAS, Lilly, S.A., MedImmune, Millennium Pharmaceuticals, Inc., Nanobiotix SA, Novartis Farmacéutica, S.A., Pfizer, S.L.U, Puma Biotechnology, Inc., Sanofi-Aventis, S.A., SFJ Pharma LTD., Teva Pharama S.L.U.; Financial Interests, Personal, Financially compensated role: BMS, Ipsen, Roche, AstraZeneca. A.P. Fay: Financial Interests, Personal, Financially compensated role: Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer Inc., Roche, Astellas Pharma, AstraZeneca, BMS, Ipsen, Janssen, MSD, Novartis, Pfizer Inc., Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Stocks/Shares: Brazilian Information Technology; Financial Interests, Personal and Institutional, Funding: AstraZeneca, Bristol Myers Squibb, CAPES-CNPq, Foundation Medicine, Ipsen, MSD, Roche. N. Matsubara: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Coordinating PI: Janssen, Roche, MSD, Taiho, Pfizer, Chugai; Financial Interests, Institutional, Local PI: AstraZeneca, Bayer, Astellas, Amgen, Eisai, Eli Lilly, AbbVie. U. De Giorgi: Financial Interests, Personal, Advisory Board: Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, EISAI, Janssen; Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Merck; Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi, Roche. P.C. Fong: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD; Financial Interests, Personal, Funding: Pfizer Inc. R.J. Jones: Financial Interests, Personal, Financially compensated role: Astellas Pharma, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Merck Serono, MSD, Pfizer, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Merck Serono, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal and Institutional, Funding: Astellas Pharma, Bayer, Clovis Oncology, Exelixis, Roche; Financial Interests, Personal, Funding, Travel: Bayer, Janssen. N.D. Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Cold Genesys, Dendreon, Exact Imaging, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Propella, Sanofi Genzyme, Speciality Networks, Tolmar, Urogen, Clarity, Lantheus, Lilly, Photocure, Telix, Photocure, Asieris, Alessa Therapeutics, Arquer, Fize medical, GConcology, Guardant, Ferring, Foundation Medicine, Immunitybio, Incyte, Minomic, NGM, Nonagen, Novartis, PlatformQ, Promaxo, Protara, Accord, Antev, Aura biosciences, Sumitomo; Financial Interests, Personal, Member of Board of Directors: Photocure, Alessa Theraputics; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Bayer, Aura, Exact Imaging, Janssen, Merck, Myovant, Novartis, Pfizer, Propella, Bristol Myers Squibb, Dendreon, Pfizer, Urogen; Financial Interests, Institutional, Local PI: Alessa, GC oncology, FORMA therapeutics, Pacific Edge, Point Biopharma, The MT group, Theralase, Verity, Astellas, Palette Life Sciences, Steba, Zenflow. C. Dunshee: Financial Interests, Personal, Advisory Board: Astellas Pharma, Bayer, Janssen, Pfizer; Financial Interests, Personal and Institutional, Funding: AstraZeneca, Bayer, Dendreon, Hengrui Pharmaceuticals, Janssen, Laekna Therapeutics, Myovant Sciences, Pfizer. S. Zschäbitz: Financial Interests, Personal and Institutional, Financially compensated role: Amgen, Astellas Pharma, Bayer, Bristol Myers Squibb, Merck Serono, MSD, Pfizer Inc.; Financial Interests, Personal, Financially compensated role: Eisai, Janssen, Novartis; Financial Interests, Personal and Institutional, Advisory Board: Amgen, Bayer, Merck Serono, MSD; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Pfizer; Financial Interests, Personal, Advisory Board: Eisai, Gilead, Ipsen, Janssen, Novartis; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Personal, Funding, Travel: Amgen, Astellas Pharma, AstraZeneca, Bayer, Ipsen, Janssen, Merck Serono, MSD, Pfizer. J. Oldenburg: Financial Interests, Personal, Financially compensated role: Astellas Pharma, AstraZeneca, Bayer, BMS Norway, Eisai, Ipsen, Janssen-Cilag, Merck, Roche; Financial Interests, Personal, Advisory Board: Astellas Pharma, AstraZeneca, Bayer, BMS, Eisai, Ipsen, Janssen-Cilag, Merck, Roche; Financial Interests, Personal, Funding, Travel: Astellas. X. Lin, D. Laird, M. Kalac, D. Kennedy: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc.; Financial Interests, Personal, Stocks or ownership: Pfizer Inc. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Personal, Advisory Board, February 2022: Arvinas; Financial Interests, Personal, Advisory Board, April 2022: Macrogenics; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the CAPITELLO 281 phase 3 trial: AstraZeneca; Non-Financial Interests, Principal Investigator, Chair of the TALAPRO-2 and TALAPRO-3 phase 3 trials: Pfizer; Non-Financial Interests, Principal Investigator, Chair of the RADIANT phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the TRITON-3 phase 3 trial: Clovis. All other authors have declared no conflicts of interest.