Abstract 618P
Background
In TITAN and SPARTAN, APA added to continuous androgen deprivation therapy (ADT) improved prostate-specific antigen (PSA) response, radiographic progression-free survival (rPFS), metastasis-free survival (MFS), and overall survival (OS) in pts with metastatic castration-sensitive prostate cancer (mCSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). We assessed efficacy and safety of APA in age groups from both studies.
Methods
mCSPC and nmCRPC pts were randomized 1:1 and 2:1 to receive APA (240 mg QD) or PBO plus ADT, and PBO-to-APA crossover after first interim analysis (IA1) was 39.5% and 19%, respectively. In this post hoc analysis, pts were stratified by age < 65, 65-79, and ≥ 80 y. Time-to-event end points were analyzed by Kaplan-Meier method and Cox proportional hazards model: rPFS and MFS at IA1 (TITAN: 22.7 mo, SPARTAN: 20.3 mo median follow-up); PSA ≥ 50% decrease from baseline (PSA50), OS, and health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy-Prostate were analyzed at final analysis (TITAN: 44 mo, SPARTAN: 52 mo median follow-up).
Results
1052 mCSPC (525 APA, 527 PBO), and 1207 nmCRPC (806 APA, 401 PBO) pts were assessed. APA added to ADT improved: PSA50 in all age groups, primary end points in all age groups but ≥80 y TITAN pts, and OS in < 65 and 65-79 y groups in TITAN and < 65 y group in SPARTAN (Table). HRQoL was maintained regardless of age or treatment group, with low side effect burden. In both studies, exposure-adjusted rates of adverse events (AEs) leading to treatment discontinuation, falls, and ischemic heart disease were increased with age regardless of treatment, and rates of skin rash were increased with age in the APA groups. Table: 618P
| Age, years | TITAN, N = 1052 | SPARTAN, N = 1207 | ||||
| <65 | 65-79 | ≥80 | <65 | 65-79 | ≥80 | |
| n (%) | 331 (31.5) | 628 (59.7) | 93 (8.8) | 149 (12.3) | 741 (61.4) | 317 (26.3) |
| Median treatment duration, mo (range) | 39.8 (1.0-52.7) | 39.8 (0-55.7) | 23.6 (2.0-48.2) | 46.2 (0.5-69.8) | 33.4 (0.3-74.5) | 20.6 (0.1-73.3) |
| APA vs PBO | ||||||
| Confirmed PSA50,a n (%) | 88.6 vs 47.3 | 90.1 vs 59.2 | 94.2 vs 58.5 | 92.5 vs 2.3 | 91.7 vs 2.0 | 84.1 vs 2.8 |
| MFS, HR (95 % CI) | NA | NA | NA | 0.14 (0.08-0.27) | 0.29 (0.23-0.37) | 0.43 (0.28-0.65) |
| rPFS, HR (95 % CI) | 0.45 (0.31-0.66) | 0.51 (0.39-0.68) | 0.55 (0.25-1.21) | NA | NA | NA |
| OS, HR (95 % CI) | 0.57 (0.40-0.80) | 0.70 (0.54-0.91) | 0.74 (0.40-1.39) | 0.39 (0.19-0.78) | 0.89 (0.69-1.16) | 0.81 (0.58-1.15) |
NA, not applicable. ap < 0.0001 for all comparisons.
Conclusions
Patients with mCSPC and nmCRPC derived clinical benefit and maintained HRQoL from APA plus ADT, but oldest pts had a trend toward less benefit with increasing age, increased AE rates, and shorter treatment duration.
Clinical trial identification
NCT02489318, NCT01946204.
Editorial acknowledgement
Writing assistance was provided by Larissa Belova, PhD, of Parexel, and was funded by Janssen Global Services, LLC.
Legal entity responsible for the study
Janssen Research & Development, LLC.
Funding
Janssen Research & Development.
Disclosure
J. Shen: Other, Personal, Advisory Board: AstraZeneca; Other, Institutional, Research Grant: Merck; Other, Institutional, Research Grant: BMS; Other, Institutional, Research Grant: Arvinas; Other, Institutional, Research Grant: MacroGenics; Other, Institutional, Research Grant: Bayer. S. Chowdhury: Financial Interests, Personal, Other, Honoraria: Astellas Pharma, Bayer, Beigene, Clovis Oncology, Janssen-Cilag, Johnson & Johnson, Novartis, Sanofi; Financial Interests, Personal, Advisory Role: Astellas Pharma, Bayer, Beigene, Clovis Onocology, Janssen-Cilag, Johnson & Johnson Novartis, Sanofi; Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma, Bayer, Beigene, Clovis Oncology, Janssen-Cilag, Johnson & Johnson, Novartis, Sanofi; Financial Interests, Personal, Funding, Research: Clovis Oncology; Financial Interests, Personal, Other, Travel, accommodations, expenses: Astellas Pharma, Bayer, Beigene, Clovis Oncology, Janssen-Cilag, Johnson & Johnson, Novartis, Sanofi. N. Agarwal: Financial Interests, Personal, Advisory Role: Astellas, AstraZeneca, Bayer, Bristol Meyers Squibb, Clovis, Eisai, Ely Lilly, EMD Serono, Exelixis, Foundation Medicine, Genetech, Janssen, Merck, Nektar, Novartis, Pfizer, Pharmacyclics, Seattle Genetics. L.I. Karsh: Financial Interests, Personal, Stocks/Shares: Swan Valley Medical; Financial Interests, Personal, Other, Honoraria: Astellas, Bayer, Janssen, Pfizer, Dendreon; Financial Interests, Personal, Advisory Role: Janssen, Pfizer, Vaxiion; Financial Interests, Personal, Speaker’s Bureau: Astellas, Bayer, Janssen, Pfizer, Clovis; Financial Interests, Personal and Institutional, Funding, Research: Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Gristol Meyers Squibb, CU Optics, CUSP, Dendreon, Epizyme, Exact Scinence, Ferring, FKD, Genetech/Roche, GenomeDX, Genomic Health, Janssen, Merck, Myovant, Nuclcix, OncoCell, MDx, Pfizer, Pharmtech/Beru; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Astellas, Bayer, Janssen, Pfizer, Dendreon. S. Oudard: Financial Interests, Personal, Advisory Role: Pfizer, Bayer, Merck, Bristol-Meyers Squibb, Novartis, Eisai, Sanofi, Janssen, Astellas Pharma, MSD Oncology, Roche, MSD oncology, Boehringer Ingelheim, Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Bayer, Merck, Bristol-yers Squibb, Novartis, Eisai, MSD Oncology, Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Pfizer, Bayer, Merck, Bristol-Myers Squibb, Novartis, Eisai, Sanofi, Astellas Pharma, Janssen, MSD, Ipsen, Roche/Genentech; Financial Interests, Personal, Funding, Research: Ipsen, Sanofi. S. Feyerabend: Financial Interests, Institutional, Advisory Role: Aventis; Financial Interests, Institutional, Advisory Role: Bayer; Financial Interests, Institutional, Advisory Role: Janssen. F. Saad: Financial Interests, Personal, Other, Honoraria: AbbVie, Amgen, Astellas, AstraZeneca, MedImmune, Bayer, Janssen, Sanofi; Financial Interests, Personal, Advisory Role: Astellas, AstraZeneca/MedImmune, Bayer, Janssen, Sanofi; Financial Interests, Personal, Funding, Research Funding: Astellas, AstraZeneca/Medimmune, Bayer, Bristol-Myers Squibb, Janssen, Pfizer, Sanofi. C.M. Pieczonka: Financial Interests, Personal, Advisory Role: Pfizer/Astellas, Bayer, Janssen Oncology, Tolmar, Sun Pharma, Dendreon, AstraZeneca, Merck, Bristol-Myers Squibb; Financial Interests, Personal, Leadership Role: Associated Medical Professionals of New York; Financial Interests, Personal, Speaker’s Bureau: Bayer, Dendreon, Pfizer, Astellas Pharma, Merck, Sun Pharma, Myovant Sciences, Tolmar, Janssen Oncology; Financial Interests, Personal, Stocks/Shares: US Urology Partners; Financial Interests, Personal, Other, Honoraria: Janssen, Dendreon, Pfizer/Astellas, Bayer, Sun Pharma, Tolmar, Myovant Sciences, Merck, AstraZeneca, Bristol-Myers Squibb; Financial Interests, Personal, Funding, Research: Bayer, Innocrin Pharma, Merck, AstraZeneca, Advantagene, Dendreon, Janssen Oncology; Financial Interests, Personal, Full or part-time Employment: Associated Medical Professionals of New York. K.N. Chi: Financial Interests, Personal, Other, ho: Janssen, Astellas, Bayer, AstraZeneca, Merck; Financial Interests, Personal, Advisory Role: Janssen, Astellas, Essa, Sanofi, Bayer, Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Merck, Bristol Myers Squibb, Point Biopharma; Financial Interests, Personal, Research Grant: Janssen, Astellas, Sanofi; Financial Interests, Institutional, Research Grant: Janssen, Astellas, Essa, Sanofi, Bayer, Roche, AstraZeneca, Novartis, Pfizer. S.D. Brookman-May: Financial Interests, Personal, Full or part-time Employment: Janssen Research & Development; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. B. Rooney: Financial Interests, Personal, Full or part-time Employment: Janssen Research & Development; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. A. Bhaumik: Financial Interests, Personal, Full or part-time Employment: Janssen Research & Development; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. A. Londhe: Financial Interests, Personal, Full or part-time Employment: Janssen Research & Development; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. S.A. McCarthy: Financial Interests, Personal, Full or part-time Employment: Janssen Research & Development; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. K.B. Bevans: Financial Interests, Personal, Full or part-time Employment: Janssen Research & Development; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. S.D. Mundle: Financial Interests, Personal, Full or part-time Employment: Janssen Research & Development; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. E.J. Small: Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Advisory Board: Fortis, Janssen; Financial Interests, Personal, Research Grant: Janssen, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen; Financial Interests, Personal, Stocks/Shares: Fortis, Harpoon Therapeutics. M.R. Smith: Financial Interests, Personal, Advisory Role: Amgen, Bayer, Janssen, Lilly, Novartis, Pfizer; Financial Interests, Personal, Research Grant: Bayer, Gilead, Janssen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen, Bayer, Janssen, Lilly. J.N. Graff: Financial Interests, Personal, Other, Consultant/Advisor: Merck, Janssen; Financial Interests, Personal, Principal Investigator: Merck, Janssen, Sanofi, Astellas; Financial Interests, Personal, Other, Scientific Study/Trial: Merck, Janssen, Sanofi, Astellas. All other authors have declared no conflicts of interest.