PRIMA/ENGOT-OV26/GOG-3012
Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
Phase 3N = 733NCT02655016
- Population
- Newly diagnosed advanced ovarian cancer in response to first-line platinum-based chemotherapy, at high risk of recurrence; 373 patients (50.9%) had tumours with HRD, 249 were HR-proficient
- Design
- Randomised, double-blind phase 3 trial. Patients with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemotherapy were randomised 2:1 to niraparib once daily or placebo; stratification by response, neoadjuvant chemotherapy and HRD status. Primary end point PFS in the HRD population and then the overall population (hierarchical testing); a prespecified interim OS analysis was done at the time of the primary PFS analysis. Primary PFS assessed by blinded independent central review.
- Primary endpoint
- PFS
- Arms
- Niraparib (experimental, n = 487): Niraparib once daily
- Placebo (control, n = 246): Placebo once daily
- People
- González-Martín A
PFSHR 0.43 (95% CI 0.31–0.59)Δ median PFS+11.5 monthsPFSHR 0.62 (95% CI 0.50–0.76)Δ median PFS+5.6 monthsOSHR 0.70 (95% CI 0.44–1.11)Δ 24-month OS+7 points
Show the numbers
| Endpoint | Analysis | Niraparib | Placebo | Effect |
|---|---|---|---|---|
| PFSTumours with HRD (n=373) | primaryGonzález-Martín 2019 | median 21.9 months | median 10.4 months | HR 0.43 (95% CI 0.31–0.59)P<0.001First step of the hierarchical primary end point. The primary PFS was assessed by blinded independent central review (stated in the 2024 final OS paper, which refers to it as previously reported). |
| PFSOverall population (n=733) | primaryGonzález-Martín 2019 | median 13.8 months | median 8.2 months | HR 0.62 (95% CI 0.50–0.76)P<0.001Primary PFS assessed by blinded independent central review (stated in the 2024 final OS paper). |
| OSOverall population (n=733) | interimGonzález-Martín 2019 | 84% at 2 y | 77% at 2 y | HR 0.70 (95% CI 0.44–1.11)Prespecified interim OS analysis at the time of the primary PFS analysis. |
| PFSHR-deficient (HRd) population (n=373) | long term-updateGonzález-Martín 2023 | median 24.5 months | median 11.2 months | HR 0.52 (95% CI 0.40–0.68)Ad hoc, investigator-assessed update with median PFS follow-up of 3.5 years. Free of progression or death at 4 years: 38% vs 17%. |
| PFSOverall population (n=733) | long term-updateGonzález-Martín 2023 | median 13.8 months | median 8.2 months | HR 0.66 (95% CI 0.56–0.79)Ad hoc, investigator-assessed update. Free of progression or death at 4 years: 24% vs 14%. |
| PFSHR-proficient (HRp) population | long term-updateGonzález-Martín 2023 | median 8.4 months | median 5.4 months | HR 0.65 (95% CI 0.49–0.87)Ad hoc, investigator-assessed update; subgroup. |
| OSOverall population (niraparib n=487, placebo n=246) | finalmedian follow-up 73.9 monthsMonk 2024 | — | — | HR 1.01 (95% CI 0.84–1.23)P=0.8834Final OS analysis after reaching 60% target maturity; hierarchical testing (overall population first). Subsequent PARP inhibitor therapy was received by 11.7% of niraparib patients and 37.8% of placebo patients in the overall population (15.8% and 48.4% in the HRd population). 5-year PFS rate: 22% vs 12% overall. |
| OSHRd population (n=373) | finalmedian follow-up 73.9 monthsMonk 2024 | — | — | HR 0.95 (95% CI 0.70–1.29)Subgroup. 5-year PFS rate numerically favoured niraparib: 35% vs 16% in the HRd population. |
| OSHR-proficient (HRp) population (n=249) | finalmedian follow-up 73.9 monthsMonk 2024 | — | — | HR 0.93 (95% CI 0.69–1.26)Subgroup. |
| Endpoint | Analysis | Niraparib | Placebo | Effect |
|---|---|---|---|---|
| PFSTumours with HRD (n=373) | primaryGonzález-Martín 2019 | median 21.9 months | median 10.4 months | HR 0.43 (95% CI 0.31–0.59)P<0.001First step of the hierarchical primary end point. The primary PFS was assessed by blinded independent central review (stated in the 2024 final OS paper, which refers to it as previously reported). |
| PFSOverall population (n=733) | primaryGonzález-Martín 2019 | median 13.8 months | median 8.2 months | HR 0.62 (95% CI 0.50–0.76)P<0.001Primary PFS assessed by blinded independent central review (stated in the 2024 final OS paper). |
| OSOverall population (n=733) | interimGonzález-Martín 2019 | 84% at 2 y | 77% at 2 y | HR 0.70 (95% CI 0.44–1.11)Prespecified interim OS analysis at the time of the primary PFS analysis. |
| PFSHR-deficient (HRd) population (n=373) | long term-updateGonzález-Martín 2023 | median 24.5 months | median 11.2 months | HR 0.52 (95% CI 0.40–0.68)Ad hoc, investigator-assessed update with median PFS follow-up of 3.5 years. Free of progression or death at 4 years: 38% vs 17%. |
| PFSOverall population (n=733) | long term-updateGonzález-Martín 2023 | median 13.8 months | median 8.2 months | HR 0.66 (95% CI 0.56–0.79)Ad hoc, investigator-assessed update. Free of progression or death at 4 years: 24% vs 14%. |
| PFSHR-proficient (HRp) population | long term-updateGonzález-Martín 2023 | median 8.4 months | median 5.4 months | HR 0.65 (95% CI 0.49–0.87)Ad hoc, investigator-assessed update; subgroup. |
| OSOverall population (niraparib n=487, placebo n=246) | finalmedian follow-up 73.9 monthsMonk 2024 | — | — | HR 1.01 (95% CI 0.84–1.23)P=0.8834Final OS analysis after reaching 60% target maturity; hierarchical testing (overall population first). Subsequent PARP inhibitor therapy was received by 11.7% of niraparib patients and 37.8% of placebo patients in the overall population (15.8% and 48.4% in the HRd population). 5-year PFS rate: 22% vs 12% overall. |
| OSHRd population (n=373) | finalmedian follow-up 73.9 monthsMonk 2024 | — | — | HR 0.95 (95% CI 0.70–1.29)Subgroup. 5-year PFS rate numerically favoured niraparib: 35% vs 16% in the HRd population. |
| OSHR-proficient (HRp) population (n=249) | finalmedian follow-up 73.9 monthsMonk 2024 | — | — | HR 0.93 (95% CI 0.69–1.26)Subgroup. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.43 | 0.31–0.59 |
| PFS | 0.62 | 0.5–0.76 |
| OS | 0.7 | 0.44–1.11 |
| PFS | 0.52 | 0.4–0.68 |
| PFS | 0.66 | 0.56–0.79 |
| PFS | 0.65 | 0.49–0.87 |
| OS | 1.01 | 0.84–1.23 |
| OS | 0.95 | 0.7–1.29 |
| OS | 0.93 | 0.69–1.26 |
- Niraparib (experimental)
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Niraparib | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 14 | 64.2% | 39.3% |
| 27 | 42.5% | 16.5% |
| 41 | 27.3% | 6.5% |
| 55 | 17.5% | 2.6% |
- Niraparib (experimental)
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Niraparib | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 9 | 63.6% | 46.7% |
| 17 | 42.6% | 23.8% |
| 26 | 27.1% | 11.1% |
| 35 | 17.2% | 5.2% |
Appears in
Sources
González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019;381(25):2391-2402.
González-Martín A, Pothuri B, Vergote I, Graybill W, Lorusso D, McCormick CC, et al. Progression-free survival and safety at 3.5years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer. Eur J Cancer. 2023;189:112908.
Monk BJ, Barretina-Ginesta MP, Pothuri B, Vergote I, Graybill W, Mirza MR, et al. Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial. Ann Oncol. 2024;35(11):981-992.