LATITUDE
Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer
Phase 3N = 1,199NCT01715285
- Population
- Men with newly diagnosed, high-risk, metastatic castration-sensitive prostate cancer
- Design
- Randomized (1:1), double-blind, placebo-controlled phase 3 trial: ADT plus abiraterone acetate 1000 mg and prednisone 5 mg daily versus ADT plus dual placebos. Eligibility required newly diagnosed metastatic castration-sensitive disease with at least two of three high-risk factors (Gleason score 8 or more, three or more bone lesions, measurable visceral metastasis). Co-primary end points: overall survival and radiographic progression-free survival.
- Primary endpoint
- OS, rPFS
- Arms
- ADT plus placebos (control, n = 602): ADT plus matching placebos
- ADT plus abiraterone acetate and prednisone (experimental, n = 597): ADT plus abiraterone acetate 1000 mg and prednisone 5 mg daily
- People
- Fizazi K, senior author Chi KN, LATITUDE Investigators
OSHR 0.62 (95% CI 0.51–0.76)rPFSHR 0.47 (95% CI 0.39–0.55)Δ median rPFS+18.2 monthsOSHR 0.66 (95% CI 0.56–0.78)Δ median OS+16.8 months
Show the numbers
| Endpoint | Analysis | ADT plus abiraterone acetate and prednisone | ADT plus placebos | Effect |
|---|---|---|---|---|
| OSRandomized patients (analysis population not stated in the NEJM abstract) | interimmedian follow-up 30.4 monthsFizazi 2017 | — | median 34.7 months | HR 0.62 (95% CI 0.51–0.76)P<0.001Planned interim analysis after 406 deaths. Median overall survival was not reached in the abiraterone group. The monitoring committee recommended unblinding and crossover. |
| rPFSRandomized patients (analysis population not stated in the NEJM abstract) | interimmedian follow-up 30.4 monthsFizazi 2017 | median 33 months | median 14.8 months | HR 0.47 (95% CI 0.39–0.55)P<0.001Hazard ratio for disease progression or death. |
| OS | finalmedian follow-up 51.8 monthsFizazi 2019 | median 53.3 months | median 36.5 months (33.5–40.0) | HR 0.66 (95% CI 0.56–0.78)P<0.0001Final analysis after 618 deaths. After the first interim analysis the study was unmasked and placebo patients could cross over to abiraterone (protocol amendment of 15 February 2017). The 95% CI for the abiraterone median is 48.2 to not reached. |
| Endpoint | Analysis | ADT plus abiraterone acetate and prednisone | ADT plus placebos | Effect |
|---|---|---|---|---|
| OSRandomized patients (analysis population not stated in the NEJM abstract) | interimmedian follow-up 30.4 monthsFizazi 2017 | — | median 34.7 months | HR 0.62 (95% CI 0.51–0.76)P<0.001Planned interim analysis after 406 deaths. Median overall survival was not reached in the abiraterone group. The monitoring committee recommended unblinding and crossover. |
| rPFSRandomized patients (analysis population not stated in the NEJM abstract) | interimmedian follow-up 30.4 monthsFizazi 2017 | median 33 months | median 14.8 months | HR 0.47 (95% CI 0.39–0.55)P<0.001Hazard ratio for disease progression or death. |
| OS | finalmedian follow-up 51.8 monthsFizazi 2019 | median 53.3 months | median 36.5 months (33.5–40.0) | HR 0.66 (95% CI 0.56–0.78)P<0.0001Final analysis after 618 deaths. After the first interim analysis the study was unmasked and placebo patients could cross over to abiraterone (protocol amendment of 15 February 2017). The 95% CI for the abiraterone median is 48.2 to not reached. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.62 | 0.51–0.76 |
| rPFS | 0.47 | 0.39–0.55 |
| OS | 0.66 | 0.56–0.78 |
- ADT plus placebos (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | ADT plus placebos |
|---|---|
| 0 | 100.0% |
| 22 | 64.4% |
| 43 | 42.4% |
| 65 | 27.3% |
| 87 | 17.6% |
- ADT plus placebos (control)
- ADT plus abiraterone acetate and prednisone (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | ADT plus placebos | ADT plus abiraterone acetate and prednisone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 21 | 37.4% | 64.3% |
| 41 | 14.7% | 42.3% |
| 62 | 5.5% | 27.2% |
| 83 | 2.1% | 17.5% |
Appears in
Sources
Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.
Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20(5):686-700.