TITAN
Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer
Phase 3N = 1,052NCT02489318
- Population
- Men with metastatic castration-sensitive prostate cancer (62.7% high-volume, 37.3% low-volume disease; 10.7% had received previous docetaxel)
- Design
- Double-blind phase 3 trial (1:1) of apalutamide 240 mg per day or placebo added to ADT. Previous treatment for localized disease and previous docetaxel were allowed. Primary end points radiographic progression-free survival and overall survival.
- Primary endpoint
- rPFS, OS
- Arms
- Placebo plus ADT (control, n = 527): Placebo plus ADT
- Apalutamide plus ADT (experimental, n = 525): Apalutamide 240 mg per day plus ADT
- People
- Chi KN, TITAN
rPFSHR 0.48 (95% CI 0.39–0.60)Δ 24-month rPFS+20.7 pointsOSHR 0.67 (95% CI 0.51–0.89)Δ 24-month OS+8.9 pointsOSHR 0.65 (95% CI 0.53–0.79)
Show the numbers
| Endpoint | Analysis | Apalutamide plus ADT | Placebo plus ADT | Effect |
|---|---|---|---|---|
| rPFSRandomized patients (analysis population not stated in the abstract) | interimmedian follow-up 22.7 monthsChi 2019 | 68.2% at 2 y | 47.5% at 2 y | HR 0.48 (95% CI 0.39–0.60)P<0.001First interim analysis; landmarks are the percentage with radiographic progression-free survival at 24 months. Hazard ratio for radiographic progression or death. |
| OSRandomized patients (analysis population not stated in the abstract) | interimmedian follow-up 22.7 monthsChi 2019 | 82.4% at 2 y | 73.5% at 2 y | HR 0.67 (95% CI 0.51–0.89)P=0.005First interim analysis; landmarks are overall survival at 24 months. |
| OSRandomized patients (N = 1,052); 405 overall survival events | finalmedian follow-up 44 monthsChi 2021 | — | median 52.2 months | HR 0.65 (95% CI 0.53–0.79)P<0.0001Final analysis after unblinding in January 2019; 208 placebo patients (39.5%) crossed over to apalutamide. Median not reached with apalutamide. The hazard ratio adjusted for crossover was 0.52 (95% CI 0.42 to 0.64). Updated without formal retesting or multiplicity adjustment. |
| Endpoint | Analysis | Apalutamide plus ADT | Placebo plus ADT | Effect |
|---|---|---|---|---|
| rPFSRandomized patients (analysis population not stated in the abstract) | interimmedian follow-up 22.7 monthsChi 2019 | 68.2% at 2 y | 47.5% at 2 y | HR 0.48 (95% CI 0.39–0.60)P<0.001First interim analysis; landmarks are the percentage with radiographic progression-free survival at 24 months. Hazard ratio for radiographic progression or death. |
| OSRandomized patients (analysis population not stated in the abstract) | interimmedian follow-up 22.7 monthsChi 2019 | 82.4% at 2 y | 73.5% at 2 y | HR 0.67 (95% CI 0.51–0.89)P=0.005First interim analysis; landmarks are overall survival at 24 months. |
| OSRandomized patients (N = 1,052); 405 overall survival events | finalmedian follow-up 44 monthsChi 2021 | — | median 52.2 months | HR 0.65 (95% CI 0.53–0.79)P<0.0001Final analysis after unblinding in January 2019; 208 placebo patients (39.5%) crossed over to apalutamide. Median not reached with apalutamide. The hazard ratio adjusted for crossover was 0.52 (95% CI 0.42 to 0.64). Updated without formal retesting or multiplicity adjustment. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| rPFS | 0.48 | 0.39–0.6 |
| OS | 0.67 | 0.51–0.89 |
| OS | 0.65 | 0.53–0.79 |
- Placebo plus ADT (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Placebo plus ADT |
|---|---|
| 0 | 100.0% |
| 33 | 64.5% |
| 65 | 42.2% |
| 98 | 27.2% |
| 131 | 17.6% |
Appears in
Sources
Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019;381(1):13-24.
Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, et al. 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;39(20):2294-2303.