1811P - Patient-reported outcomes (PROs) in men with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations receiving talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA: Results from a phase III (TALAPRO-2) study

Background

TALAPRO-2 (NCT03395197) showed statistically significant improvement in imaging-based progression-free survival with TALA + ENZA (n=200) vs PBO + ENZA (n=199) (HR=0.45; 95% CI 0.33–0.61; P<0.0001) in men with HRR mutations receiving first-line treatment for mCRPC. Here we report PRO data for this HRR mutation cohort.

Methods

PROs were assessed at day 1 and scheduled visits (every 4 weeks until week 53, then every 8 weeks) until radiographic progression using the EORTC QLQ-C30 and its prostate cancer module, QLQ-PR25. Prespecified PRO endpoints included overall mean change from baseline (per longitudinal repeated measures mixed-effects model) and time to definitive deterioration (TTD) with a clinically meaningful change of ≥10-points. Stratified log-rank test and Cox proportional hazards model were used to make TTD between-arm comparisons.

Results

Of the 399 men in the HRR mutation cohort, 394 (n=197 both arms) had at least a baseline plus 1 post-baseline PRO score. No statistically significant difference in treatment effect on the global health status (GHS)/quality of life (QoL) scale was observed between arms. The treatment effect on the physical, emotional, and cognitive functioning scales favored TALA + ENZA, but did not meet the clinical meaningful threshold (Table). A longer TTD for TALA + ENZA vs PBO + ENZA was observed in GHS/QoL (HR=0.69; 95% CI 0.49–0.97; P=0.032; median 27.1 vs 19.3 months) and urinary symptoms (HR=0.56; 95% CI 0.34–0.93; P=0.022; median not reached vs 30.2 months). Table: 1811P

Overall change from baseline in PROs

Positive scores indicate better GHS/QoL and functioning *Did not meet the predefined threshold of clinical meaningfulness

Conclusions

TTD in GHS/QoL and urinary symptoms were significantly longer with TALA + ENZA vs PBO + ENZA. Modest treatment differences favoring TALA + ENZA vs PBO + ENZA were observed for some functioning scales. These data complement the benefit–risk assessment of TALAPRO-2 for men with mCRPC who have HRR mutations.

Clinical trial identification

NCT03395197.

Editorial acknowledgement

Medical writing and editorial assistance were provided by Michelle Mancher, MPH, and Rosie Henderson of Onyx (a Prime Global agency), and was funded by Pfizer Inc.

Legal entity responsible for the study

Pfizer Inc. and Astellas Pharma Inc.

Funding

Pfizer Inc. and Astellas Pharma Inc.

Disclosure

A.P. Fay: Financial Interests, Institutional, Other, Honoraria: AstraZeneca, BMS, Ipsen, Janssen Pharmaceuticals, MSD, Novartis, Pfizer Inc., Roche; Financial Interests, Institutional, Speaker, Consultant, Advisor: AstraZeneca, Ipsen, Merck Sharp & Dohme, Novartis, Pfizer Inc., Roche. K. Fizazi: Financial Interests, Institutional, Other, Honoraria: Astellas Pharma Inc., Bayer, Janssen Pharmaceuticals, Sanofi; Financial Interests, Institutional, Speaker, Consultant, Advisor: Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, BMS, Clovis Oncology, ESSA, Janssen Pharmaceuticals, Novartis, Orion Pharma, Ltd., Pfizer Inc., Sanofi; Financial Interests, Personal, Other, Travel expenses: AstraZeneca, Janssen Pharmaceuticals, MSD. N. Matsubara: Financial Interests, Institutional, Other, Honoraria: Sanofi; Financial Interests, Institutional, Speaker, Consultant, Advisor: Amgen, AstraZeneca, Janssen Pharmaceuticals, Eli Lilly and Co., Pfizer Inc., Sanofi, Seagen; Financial Interests, Institutional, Research Funding: AbbVie, Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Eisai Co., Ltd., Janssen Pharmaceuticals, Eli Lilly and Co., MSD, Novartis, Roche/Genentech, Seagen, Takeda Inc.. A.A. Azad: Financial Interests, Institutional, Other, Honoraria: Aculeus Therapeutics, Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, BMS, Ipsen, Janssen Pharmaceuticals, Merck Serono, Merck Sharp & Dohme, Novartis, Noxopharm, Ltd., Pfizer Inc., Sanofi, Telix Pharmaceuticals, Tolmar Inc; Financial Interests, Institutional, Speaker, Consultant, Advisor: Aculeus Therapeutics, Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, BMS, Ipsen, Janssen Pharmaceuticals, Merck Serono, Merck Sharp & Dohme, Novartis, Noxopharm, Ltd., Pfizer Inc., Sanofi, Telix Pharmaceuticals, Tolmar Inc; Financial Interests, Institutional, Speaker’s Bureau: Amgen, Astellas Pharma Inc., Bayer, BMS, Ipsen, Janssen Pharmaceuticals, Merck Serono, Novartis; Financial Interests, Institutional, Research Funding: Aptevo Therapeutics, Astellas Pharma Inc., AstraZeneca, Bionomics, Ltd., BMS, Exelixis, Gilead Sciences Inc, GSK plc, Hinova Pharmaceuticals, Ipsen, Janssen Pharmaceuticals, Eli Lilly and Co., MedImmune, Merck Serono, MSD, Novartis, Pfizer Inc., Sanofi, Synthorx Inc; Financial Interests, Personal, Other, Travel expenses: Amgen, Astellas Pharma Inc., Bayer, Janssen Pharmaceuticals, Merck Serono, Pfizer Inc., Sanofi, Tolmar Inc. F. Saad: Financial Interests, Institutional, Other, Travel expenses: Astellas Pharma Inc., Janssen Oncology, Sanofi, Bayer, AstraZeneca; Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., Janssen Oncology, Sanofi, AstraZeneca/MedImmune; Financial Interests, Institutional, Funding, Institutional funding: Astellas Pharma Inc., Bayer, Janssen Oncology, Sanofi, AstraZeneca. U.F.F. De Giorgi: Financial Interests, Institutional, Speaker, Consultant, Advisor: Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, BMS, Clovis Oncology, Dompé Farmaceutici, Eisai Co., Ltd., Ipsen, Janssen Pharmaceuticals, Merck KGaA, MSD, Novartis, Pfizer Inc., PharmaMar; Financial Interests, Institutional, Research Funding: AstraZeneca, Roche, Sanofi; Financial Interests, Personal, Other, Travel expenses: Ipsen, Pfizer Inc.. J.Y. Joung: Financial Interests, Institutional, Other, Honoraria: Astellas Pharma Inc., Johnson & Johnson/Janssen Pharmaceuticals, Sanofi. P.C. Fong: Financial Interests, Institutional, Speaker, Consultant, Advisor: MSD; Financial Interests, Personal, Other, Travel expenses: Pfizer Inc.. R.J. Jones: Financial Interests, Institutional, Other, Honoraria: Astellas Pharma Inc., Bayer, BMS, Ipsen, Janssen Pharmaceuticals, Merck Serono, MSD, Pfizer Inc., Roche; Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., Bayer, BMS, Ipsen, Janssen Pharmaceuticals, Merck Serono, MSD, Novartis, Pfizer Inc., Roche; Financial Interests, Institutional, Research Funding: Astellas Pharma Inc., Bayer, Clovis Oncology, Exelis. S. Zschäbitz: Financial Interests, Institutional, Advisory Role: Amgen, Bayer, BMS, Eisai Co., Ltd., Janssen Pharmaceuticals, MSD, Novartis, Pfizer Inc.; Financial Interests, Institutional, Other, Honoraria: Amgen, Bayer, BMS, Eisai Co., Ltd., Janssen Pharmaceuticals, MSD, Novartis, Pfizer Inc.; Financial Interests, Institutional, Research Funding: Eisai Co., Ltd.; Financial Interests, Personal, Other, Travel expenses: Amgen, Astellas Pharma Inc., AstraZeneca, Ipsen, Janssen Pharmaceuticals, Merck, MSD, Pfizer Inc.. J. Oldenburg: Financial Interests, Institutional, Other, Honoraria: BMS Norway; Financial Interests, Institutional, Speaker, Consultant, Advisor: BMS Norway; Financial Interests, Institutional, Research Funding: BMS Norway; Financial Interests, Institutional, Speaker’s Bureau: Astellas Pharma Inc.. N.D. Shore: Financial Interests, Institutional, Speaker, Consultant, Advisor: AbbVie, Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, Boston Scientific, BMS/Sanofi, CG Oncology Inc, Clarity Pharmaceuticals, Clovis Oncology, Dendreon, Exact Imaging, Exact Sciences Corp., FerGene, Ferring Pharmaceuticals, Foundation Medicine, Genesis Cancer Care, Genzyme, Invitae Corp., Janssen Pharmaceuticals, Lantheus Medical Imaging, Eli Lilly and Co., MDxHealth, Medivation, Merck, Myovant Sciences, Myriad Genetics Inc, Nymox Pharmaceutical Corporation, Pacific Edge Limited, Peerview, Pfizer Inc., Phosphorus, Photocure, Propella Therapeutics, Sanofi, Sema4, Sesen Bio, Speciality Networks, Telix Pharmaceuticals, Tempus, Tolmar Inc, Urogen Pharma, Vaxiion Therapeutics; Financial Interests, Institutional, Speaker’s Bureau: Astellas Pharma Inc., AstraZeneca, Bayer, Clovis Oncology, Dendreon, Foundation Medicine, Guardant Health, Janssen Pharmaceuticals, Merck, Pfizer Inc.; Financial Interests, Institutional, Research Funding: AbbVie, Advantagene Inc, Amgen, Aragon Pharmaceuticals, Astellas Pharma Inc., AstraZeneca, Bayer, Boston Scientific, BMS/Pfizer, CG Oncology, Clovis Oncology, Dendreon, DisperSol Technologies, Endocyte, Exact Imaging, Exelixis, Ferring Pharmaceuticals, FKD Therapies, FORMA Therapeutics, Foundation Medicine, Genentech Inc, Guardant Health, Invitae Corp., Istari Oncology, Janssen Pharmaceuticals, Jiangsu Yahong Meditech Co., Ltd., MDxHealth, Medivation, Merck, MT Group, Myovant Sciences, Myriad Genetics, Novartis, Nymox Pharmaceutical Corporation, OncoCell MDx, ORIC Pharmaceuticals, Pacific Edge Limited, Palette Life Sciences, Pfizer Inc., Plexxikon, POINT Biopharma, Propella Therapeutics, RhoVac, Sanofi, Seagen, Sesen Bio; Financial Interests, Institutional: Steba Biotech. C. Dunshee: Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., Bayer, Janssen Biotech, Pfizer Inc.; Financial Interests, Institutional, Research Funding: AstraZeneca, Dendreon, Eleven Biotherapeutics, Jiangsu Hengrui, Janssen Pharmaceuticals, Laekna Therapeutics, Myovant Sciences, Pfizer Inc., Tavanta Therapeutics. J. Carles Galceran: Financial Interests, Institutional, Speaker, Consultant, Advisor: Advanced Accelerator Applications/Novartis, Astellas Pharma Inc., AstraZeneca, Bayer, BMS, Johnson & Johnson/Janssen, MSD Oncology, Pfizer Inc., Roche, Sanofi; Financial Interests, Institutional, Speaker’s Bureau: Astellas Pharma Inc., Bayer, Johnson & Johnson; Financial Interests, Institutional, Research Funding: AB Science, Aragon Pharmaceuticals Inc, Arog Pharmaceuticals, Astellas Pharma Inc., AstraZeneca, AVEO Oncology, Bayer, Blueprint Medicines, BN ImmunoTherapeutics, Boehringer Ingelheim, BMS International Corporation, Clovis Oncology, Cougar Biotechnology, Deciphera, Exelixis, Genentech, GSK, Incyte, Janssen Cilag International NV, Karyopharm Therapeutics, Laboratories Leurquin Mediolanum, Eli Lilly and Co., Medimmune, Millennium Pharmaceuticals, Nanobiotix, Novartis Farmacéutica SA, Pfizer Inc., Puma Biotechnology, Roche, Sanofi, SFJ Pharmaceuticals Inc, Teva Pharmaceutical Industries Ltd.; Financial Interests, Institutional, Other, Travel expenses: AstraZeneca, BMS, Ipsen, Roche. P. Cislo, J. Chang, C.G. Healy, A. Niyazov: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc.. N. Agarwal: Financial Interests, Institutional, Speaker, Consultant, Advisor: Astellas Pharma Inc., AstraZeneca, AVEO Oncology, Bayer, BMS, Calithera Biosciences, Eisai Co., Ltd., EMD Serono, Exelixis, Foundation Medicine, Genentech Inc, Gilead Sciences Inc, Janssen Pharmaceuticals, Eli Lilly and Co., Medivation, MEI Pharma Inc, Merck, Nektar Therapeutics, Novartis AG, Pfizer Inc., Pharmacyclics, Seagen; Financial Interests, Institutional, Research Funding: Amgen, Arvinas, AstraZeneca, Bayer, BMS, Calithera Biosciences, Celldex Therapeutics Inc, CRISPR Therapeutics, Eisai Co., Ltd., Exelixis, Genentech Inc, Immunomedics Inc, Janssen Pharmaceuticals, Eli Lilly and Co., Merck, Nektar Therapeutics, ORIC Pharmaceuticals, Pfizer Inc., Takeda Inc..