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Clinical Trial
. 2021 Jul 10;39(20):2294-2303.
doi: 10.1200/JCO.20.03488. Epub 2021 Apr 29.

Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study

Kim N Chi  1 , Simon Chowdhury  2 , Anders Bjartell  3 , Byung Ha Chung  4 , Andrea J Pereira de Santana Gomes  5 , Robert Given  6 , Alvaro Juárez  7 , Axel S Merseburger  8 , Mustafa Özgüroğlu  9 , Hirotsugu Uemura  10 , Dingwei Ye  11 , Sabine Brookman-May  12   13 , Suneel D Mundle  13 , Sharon A McCarthy  13 , Julie S Larsen  14 , Weili Sun  14 , Katherine B Bevans  15 , Ke Zhang  16 , Nibedita Bandyopadhyay  13 , Neeraj Agarwal  17
Affiliations
Clinical Trial

Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study

Kim N Chi et al. J Clin Oncol. .

Abstract

Purpose: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover.

Methods: Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed.

Results: With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached v 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; P < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance (P < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports.

Conclusion: The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.

Trial registration: ClinicalTrials.gov NCT02489318.

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Conflict of interest statement

Kim N. ChiHonoraria: Janssen, Astellas Pharma, Bayer, AstraZeneca, Roche, MerckConsulting or Advisory Role: ESSA, Astellas Pharma, Janssen, Sanofi, Amgen, Bayer, AstraZeneca, Roche, POINT Biopharma, Daiichi Sankyo, Merck, Constellation PharmaceuticalsResearch Funding: Janssen, Astellas Pharma, Bayer, Sanofi, Bristol Myers Squibb, Merck, Roche, AstraZeneca, Novartis, Pfizer, ESSA Simon ChowdhuryHonoraria: Clovis Oncology, NovartisConsulting or Advisory Role: Clovis Oncology, Astellas Pharma, Bayer, Pfizer, Janssen-Cilag, BeiGene, NovartisSpeakers' Bureau: Pfizer, Janssen-CilagResearch Funding: Sanofi-Aventis Anders BjartellConsulting or Advisory Role: Astellas Pharma, Bayer, Janssen-Cilag, AstraZeneca, Merck, SandozSpeakers' Bureau: Astellas Pharma, Bayer, Janssen-CilagResearch Funding: Ferring, Astellas Pharma, BayerTravel, Accommodations, Expenses: Astellas Pharma, Bayer, Janssen-Cilag Byung Ha ChungHonoraria: Astellas Pharma, Ipsen, JW Pharmaceutical, TakedaConsulting or Advisory Role: Janssen, Bayer, Pfizer, AstraZeneca, Roche, Myovant Sciences Robert GivenConsulting or Advisory Role: Janssen OncologySpeakers' Bureau: Janssen Oncology, Bayer Schering Pharma, Myovant Sciences Alvaro Juárez SotoHonoraria: Astellas Pharma, Janssen Oncology, Pfizer, BayerConsulting or Advisory Role: Janssen OncologyResearch Funding: Janssen Oncology, Bayer, Exelixis Axel S. MerseburgerHonoraria: Janssen-Cilag, Astellas Pharma, Ipsen, Roche, Bristol Myers Squibb, Eisai, Takeda, Pfizer, NovartisConsulting or Advisory Role: MSD Oncology, Bristol Myers Squibb, Janssen-Cilag, Astellas Pharma, Ipsen, Clovis OncologySpeakers' Bureau: IpsenResearch Funding: Novartis, AstraZeneca, Janssen-Cilag, Bristol Myers Squibb, Clovis OncologyTravel, Accommodations, Expenses: Janssen-Cilag, Astellas Pharma, Ipsen Mustafa ÖzgüroğluHonoraria: Astellas Pharma, Novartis, Janssen OncologyConsulting or Advisory Role: MSD Oncology, AstraZenecaSpeakers' Bureau: AstraZenecaTravel, Accommodations, Expenses: AstraZeneca Hirotsugu UemuraConsulting or Advisory Role: Sanofi, Pfizer, JanssenSpeakers' Bureau: Pfizer, Bristol Myers Squibb, Janssen, BayerResearch Funding: Astellas Pharma, Takeda, AstraZeneca, Sanofi, Ono Pharmaceutical, Daiichi Sankyo/UCB Japan, Kissei Pharmaceutical Sabine Brookman-MayEmployment: Janssen Research & DevelopmentLeadership: Janssen Research & DevelopmentStock and Other Ownership Interests: Johnson & Johnson Suneel D. MundleEmployment: Janssen Research & DevelopmentStock and Other Ownership Interests: Johnson & Johnson Sharon A. McCarthyEmployment: Janssen OncologyStock and Other Ownership Interests: Johnson and Johnson Julie S. LarsenEmployment: Janssen Research & DevelopmentStock and Other Ownership Interests: Johnson and Johnson Weili SunEmployment: Janssen OncologyStock and Other Ownership Interests: Johnson and Johnson Katherine B. BevansEmployment: JanssenStock and Other Ownership Interests: Johnson and Johnson Ke ZhangEmployment: Janssen Research & DevelopmentStock and Other Ownership Interests: Johnson and Johnson Nebita BandyopadhyayEmployment: Janssen Research & DevelopmentStock and Other Ownership Interests: Johnson and Johnson Neeraj AgarwalConsulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Foundation One Inc, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, GenentechResearch Funding: Bayer, Bristol Myers Squibb, GlaxoSmithKline, Takeda, Novartis, Pfizer, BN ImmunoTherapeutics, Exelixis, TRACON Pharmaceuticals, Rexahn Pharmaceuticals, Amgen, AstraZeneca, Active Biotech, Bavarian Nordic, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Newlink Genetics, Prometheus, SanofiNo other potential conflicts of interest were reported.

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