A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC
Summary
The purpose of this study is to determine if the addition of apalutamide to ADT provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for participants with mHSPC.
Timeline
- Start
- 2015-11-27
- Primary completion
- 2020-09-07
- Completion
- 2027-12-31
Outcome
Met primary endpoint
registry analysis (superiority test); Placebo + Androgen Deprivation Therapy (ADT) vs Apalutamide + ADT; p <0.0001; Hazard Ratio (HR) 0.484 (95% CI 0.391 to 0.600); Log Rank NCT02489318 ↗
registry analysis (superiority test); Placebo + Androgen Deprivation Therapy (ADT) vs Apalutamide + ADT; p <0.0001; Hazard Ratio (HR) 0.651 (95% CI 0.534 to 0.793); Log Rank NCT02489318 ↗
paper overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT PMID 31150574 ↗
release “Phase 3 TITAN Study Unblinded as Dual Primary Endpoints Achieved” jnj.com ↗
release “TITAN, which met its dual primary endpoints, overall survival (OS) and radiographic progression-free survival (rPFS).” jnj.com ↗
release “In the TITAN study, ERLEADA®plus ADT significantly extended OS compared to placebo plus ADT with a 33 percent reduction in the risk of death” jnj.com ↗
release “ERLEADA®plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent lower risk of radiographic progression or death” jnj.com ↗
release “Phase 3 TITAN study confirmed that ERLEADA®plus ADT provided a statistically significant improvement in OS” jnj.com ↗
release “TITAN demonstrated a statistically significant superior overall survival benefit of ERLEADA® plus androgen deprivation therapy (ADT) compared to ADT alone at the primary analysis” jnj.com ↗
Publications
- Hori T, Iwamoto H, Inaba T, Nakagawa R, Kamijima T, Kano H, Makino T, Naito R, Yaegashi H, Shigehara K, Nohara T, Izumi K, Mizokami A. Association Between Castration-resistant Prostate Cancer Progression Patterns and Survival Outcomes in Metastatic Castration-sensitive Prostate Cancer: A Post Hoc Analysis of the TITAN Trial. Eur Urol Focus. 2026 Sep 11:S2405-4569(26)00149-5. doi: 10.1016/j.euf.2026.07.003. Online ahead of print.
- Hori T, Iwamoto H, Inaba T, Nakagawa R, Kamijima T, Makino T, Naito R, Kadomoto S, Yaegashi H, Shigehara K, Nohara T, Izumi K, Mizokami A. Integrating NCCN and LATITUDE in metastatic castration-sensitive prostate cancer: a TITAN analysis. World J Urol. 2026 Aug 19;44(1):585. doi: 10.1007/s00345-026-06695-5.
- Karsh LI, Bevans KB, Saad F, Chung BH, Oudard S, Brookman-May SD, McCarthy SA, Smith MR, Chi KN, Small EJ, Agarwal N. Prostate-specific antigen and health-related quality of life in individuals with advanced prostate cancer treated with apalutamide: a plain language summary of the SPARTAN and TITAN studies. Future Oncol. 2024;20(35):2689-2698. doi: 10.1080/14796694.2024.2384257. Epub 2024 Aug 20.
- Roy S, Sun Y, Chi KN, Ong M, Malone S, Wallis CJD, Kishan AU, Malone J, Swami U, Gebrael G, Brown JR, Jia AY, Morgan SC, Saad F, Chowdhury S, Agarwal N, Spratt DE. Early Prostate-Specific Antigen Response by 6 Months Is Predictive of Treatment Effect in Metastatic Hormone Sensitive Prostate Cancer: An Exploratory Analysis of the TITAN Trial. J Urol. 2024 Nov;212(5):672-681. doi: 10.1097/JU.0000000000004158. Epub 2024 Jul 26.
- Merseburger AS, Agarwal N, Bjartell A, Uemura H, Soto AJ, Bhaumik A, Bohm J, Tran N, Krochmann N, Nematian-Samani M, Mundle SD, Brookman-May SD, Lopez-Gitlitz A, McCarthy SA, Chi K, Chowdhury S. Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) study: ultralow prostate-specific antigen decline with apalutamide plus androgen-deprivation therapy. BJU Int. 2024 Dec;134(6):982-991. doi: 10.1111/bju.16449. Epub 2024 Jun 28.
- Shen J, Chowdhury S, Agarwal N, Karsh LI, Oudard S, Gartrell BA, Feyerabend S, Saad F, Pieczonka CM, Chi KN, Brookman-May SD, Rooney B, Bhaumik A, McCarthy SA, Bevans KB, Mundle SD, Small EJ, Smith MR, Graff JN. Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN. Br J Cancer. 2024 Jan;130(1):73-81. doi: 10.1038/s41416-023-02492-8. Epub 2023 Nov 11.
- Merseburger AS, Agarwal N, Bhaumik A, Lefresne F, Karsh LI, Pereira de Santana Gomes AJ, Soto AJ, Given RW, Brookman-May SD, Mundle SD, McCarthy SA, Uemura H, Chowdhury S, Chi KN, Bjartell A. Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study. Eur J Cancer. 2023 Nov;193:113290. doi: 10.1016/j.ejca.2023.113290. Epub 2023 Aug 11.
- Agarwal N, McQuarrie K, Bjartell A, Chowdhury S, Pereira de Santana Gomes AJ, Chung BH, Ozguroglu M, Juarez Soto A, Merseburger AS, Uemura H, Ye D, Given R, Basch E, Miladinovic B, Lopez-Gitlitz A, Chi KN. Apalutamide plus Androgen Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer: Analysis of Pain and Fatigue in the Phase 3 TITAN Study. J Urol. 2021 Oct;206(4):914-923. doi: 10.1097/JU.0000000000001841. Epub 2021 May 27.
- Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juarez A, Merseburger AS, Ozguroglu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. doi: 10.1200/JCO.20.03488. Epub 2021 Apr 29.
- Uemura H, Koroki Y, Iwaki Y, Imanaka K, Kambara T, Lopez-Gitlitz A, Smith A, Uemura H. Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study. BMC Urol. 2020 Sep 2;20(1):139. doi: 10.1186/s12894-020-00689-0.
- Agarwal N, McQuarrie K, Bjartell A, Chowdhury S, Pereira de Santana Gomes AJ, Chung BH, Ozguroglu M, Juarez Soto A, Merseburger AS, Uemura H, Ye D, Given R, Cella D, Basch E, Miladinovic B, Dearden L, Deprince K, Naini V, Lopez-Gitlitz A, Chi KN; TITAN investigators. Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2019 Nov;20(11):1518-1530. doi: 10.1016/S1470-2045(19)30620-5. Epub 2019 Sep 29.
- Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juarez Soto A, Merseburger AS, Ozguroglu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. doi: 10.1056/NEJMoa1903307. Epub 2019 May 31.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Apalutamide | Small molecule | 240 mg | Oral |