PROpel
Abiraterone and olaparib versus abiraterone and placebo as first-line therapy for metastatic castration-resistant prostate cancer
Phase 3NCT03732820
- Population
- First-line metastatic castration-resistant prostate cancer, enrolled irrespective of HRR gene mutation status
- Design
- Double-blind, randomised (1:1) phase 3 trial of abiraterone 1000 mg once daily plus prednisone or prednisolone with olaparib 300 mg twice daily or placebo, as first-line therapy for mCRPC. Patients were enrolled regardless of homologous recombination repair gene mutation (HRRm) status, which was determined after enrolment by tumour tissue and circulating tumour DNA tests. The primary endpoint was imaging-based progression-free survival by investigator assessment; overall survival was a key secondary endpoint with alpha control (alpha threshold at the final analysis 0.0377, two-sided). The final analysis randomised 399 patients to olaparib plus abiraterone and 397 to placebo plus abiraterone.
- Primary endpoint
- rPFS
- Arms
- Olaparib plus abiraterone (experimental, n = 399): Olaparib 300 mg twice daily plus abiraterone 1000 mg once daily plus prednisone or prednisolone
- Placebo plus abiraterone (control, n = 397): Placebo plus abiraterone 1000 mg once daily plus prednisone or prednisolone
- People
- Clarke NW
rPFSHR 0.66 (95% CI 0.54–0.81)Δ median rPFS+8.2 monthsrPFSHR 0.61 (95% CI 0.49–0.74)OSHR 0.86 (95% CI 0.66–1.12)OSHR 0.81 (95% CI 0.67–1.00)Δ median OS+7.4 months
Show the numbers
| Endpoint | Analysis | Olaparib plus abiraterone | Placebo plus abiraterone | Effect |
|---|---|---|---|---|
| rPFSAll enrolled patients, irrespective of HRR gene mutation statusImaging-based progression-free survival (ibPFS) by investigator assessment | primaryClarke 2022 | median 24.8 months | median 16.6 months | HR 0.66 (95% CI 0.54–0.81)P<0.001Planned primary analysis at the first data cutoff. |
| rPFSAll enrolled patients, irrespective of HRR gene mutation statusImaging-based progression-free survival by blinded independent central review | primaryClarke 2022 | — | — | HR 0.61 (95% CI 0.49–0.74)Reported as consistent with the investigator-assessed result; no medians or p-value are given in the abstract. |
| OSAll enrolled patients, irrespective of HRR gene mutation status | interimClarke 2022 | — | — | HR 0.86 (95% CI 0.66–1.12)P=0.29Overall survival data were immature at the first data cutoff (28.6% maturity). |
| OS | finalmedian follow-up 36.6 monthsSaad 2023 | median 42.1 months | median 34.7 months (31.0–39.3) | HR 0.81 (95% CI 0.67–1.00)P=0.054Final prespecified overall survival analysis; the alpha threshold was 0.0377 (two-sided), so the difference was not statistically significant. The 95% CI for the olaparib plus abiraterone median is 38.4 to not reached. Median follow-up for overall survival in patients with censored data was 36.6 months (olaparib) and 36.5 months (placebo). |
| Endpoint | Analysis | Olaparib plus abiraterone | Placebo plus abiraterone | Effect |
|---|---|---|---|---|
| rPFSAll enrolled patients, irrespective of HRR gene mutation statusImaging-based progression-free survival (ibPFS) by investigator assessment | primaryClarke 2022 | median 24.8 months | median 16.6 months | HR 0.66 (95% CI 0.54–0.81)P<0.001Planned primary analysis at the first data cutoff. |
| rPFSAll enrolled patients, irrespective of HRR gene mutation statusImaging-based progression-free survival by blinded independent central review | primaryClarke 2022 | — | — | HR 0.61 (95% CI 0.49–0.74)Reported as consistent with the investigator-assessed result; no medians or p-value are given in the abstract. |
| OSAll enrolled patients, irrespective of HRR gene mutation status | interimClarke 2022 | — | — | HR 0.86 (95% CI 0.66–1.12)P=0.29Overall survival data were immature at the first data cutoff (28.6% maturity). |
| OS | finalmedian follow-up 36.6 monthsSaad 2023 | median 42.1 months | median 34.7 months (31.0–39.3) | HR 0.81 (95% CI 0.67–1.00)P=0.054Final prespecified overall survival analysis; the alpha threshold was 0.0377 (two-sided), so the difference was not statistically significant. The 95% CI for the olaparib plus abiraterone median is 38.4 to not reached. Median follow-up for overall survival in patients with censored data was 36.6 months (olaparib) and 36.5 months (placebo). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| rPFS | 0.66 | 0.54–0.81 |
| rPFS | 0.61 | 0.49–0.74 |
| OS | 0.86 | 0.66–1.12 |
| OS | 0.81 | 0.67–1 |
- Olaparib plus abiraterone (experimental)
- Placebo plus abiraterone (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Olaparib plus abiraterone | Placebo plus abiraterone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 16 | 63.9% | 51.3% |
| 31 | 42.0% | 27.4% |
| 47 | 26.9% | 14.1% |
| 62 | 17.7% | 7.5% |
- Olaparib plus abiraterone (experimental)
- Placebo plus abiraterone (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Olaparib plus abiraterone | Placebo plus abiraterone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 26 | 65.2% | 59.5% |
| 53 | 41.8% | 34.7% |
| 79 | 27.2% | 20.6% |
| 105 | 17.8% | 12.3% |
Appears in
Sources
Clarke NW, Armstrong AJ, Thiery-Vuillemin A, Oya M, Shore N, Loredo E, et al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evid. 2022;1(9):EVIDoa2200043.
Saad F, Clarke NW, Oya M, Shore N, Procopio G, Guedes JD, et al. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24(10):1094-1108.