Kim N Chi1, Simon Chowdhury2, Anders Bjartell3, Byung Ha Chung4, Andrea J Pereira de Santana Gomes5, Robert Given6, Alvaro Juárez7, Axel S Merseburger8, Mustafa Özgüroğlu9, Hirotsugu Uemura10, Dingwei Ye11, Sabine Brookman-May12,13, Suneel D Mundle13, Sharon A McCarthy13, Julie S Larsen14, Weili Sun14, Katherine B Bevans15, Ke Zhang16, Nibedita Bandyopadhyay13, Neeraj Agarwal17. 1. BC Cancer and Vancouver Prostate Centre, Vancouver, BC, Canada. 2. Guy's and St Thomas' Hospitals, London, United Kingdom. 3. Skåne University Hospital, Lund University, Malmö, Sweden. 4. Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. 5. Liga Norte Riograndense Contra O Cancer, Natal, Brazil. 6. Urology of Virginia, Eastern Virginia Medical School, Norfolk, VA. 7. Hospital Universitario de Jerez de la Frontera, Cadiz, Spain. 8. University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. 9. Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey. 10. Kindai University Hospital Faculty of Medicine, Osaka, Japan. 11. Fudan University Shanghai Cancer Center, Shanghai, China. 12. Ludwig-Maximilians-University (LMU), Munich, Germany. 13. Janssen Research & Development, Spring House, PA. 14. Janssen Research & Development, Los Angeles, CA. 15. Janssen Research & Development, Horsham, PA. 16. Janssen Research & Development, San Diego, CA. 17. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
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 ongoingandrogen 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.
RCT Entities:
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.
Authors: Rushikesh Potdar; Benjamin A Gartrell; Robert Given; Lawrence Karsh; Jeffrey Frankel; Karen Nenno; Kris O'MalleyLeFebvre; Amitabha Bhaumik; Sharon McCarthy; Tracy McGowan; Christopher Pieczonka Journal: Am J Cancer Res Date: 2022-01-15 Impact factor: 6.166
Authors: Anil Kapoor; Tamim Niazi; Krista Noonan; Ricardo A Rendon; Nimira Alimohamed; Wassim Kassouf; Alejandro Berlin; William Chu; Christian Kollmannsberger; Alan I So Journal: Can Urol Assoc J Date: 2022-04 Impact factor: 2.052