PAOLA-1
Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer
Phase 3N = 806NCT02477644
- Population
- Newly diagnosed advanced high-grade ovarian cancer in response to first-line platinum-taxane chemotherapy plus bevacizumab, regardless of surgical outcome or BRCA mutation status
- Design
- Randomised, double-blind, international phase 3 trial. Patients with newly diagnosed advanced high-grade ovarian cancer responding to first-line platinum-taxane chemotherapy plus bevacizumab, regardless of surgical outcome or BRCA status, were randomised 2:1 to olaparib tablets 300 mg twice daily for up to 24 months or placebo; all received bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. Primary end point investigator-assessed PFS.
- Primary endpoint
- PFS
- Arms
- Olaparib plus bevacizumab (experimental, n = 537): Olaparib 300 mg twice daily for up to 24 months plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months
- Placebo plus bevacizumab (control, n = 269): Placebo for up to 24 months plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months
- People
- Ray-Coquard I
PFSHR 0.59 (95% CI 0.49–0.72)Δ median PFS+5.5 monthsPFSHR 0.33 (95% CI 0.25–0.45)Δ median PFS+19.5 monthsPFSHR 0.43 (95% CI 0.28–0.66)Δ median PFS+11.5 months
Show the numbers
| Endpoint | Analysis | Olaparib plus bevacizumab | Placebo plus bevacizumab | Effect |
|---|---|---|---|---|
| PFSRandomised patients (N=806); analysis population not stated in the abstract | primarymedian follow-up 22.9 monthsRay-Coquard 2019 | median 22.1 months | median 16.6 months | HR 0.59 (95% CI 0.49–0.72)P<0.001Investigator-assessed. |
| PFSHRD-positive tumours, including those with BRCA mutations | exploratorymedian follow-up 22.9 monthsRay-Coquard 2019 | median 37.2 months | median 17.7 months | HR 0.33 (95% CI 0.25–0.45)The 2023 report describes the biomarker analyses as prespecified and exploratory. |
| PFSHRD-positive tumours without a BRCA mutation | exploratorymedian follow-up 22.9 monthsRay-Coquard 2019 | median 28.1 months | median 16.6 months | HR 0.43 (95% CI 0.28–0.66)Exploratory subgroup. |
| OS | finalRay-Coquard 2023 | median 56.5 months | median 51.6 months | HR 0.92 (95% CI 0.76–1.12)P=0.4118Median follow-up 61.7 months (olaparib) and 61.9 months (placebo). Subsequent PARP inhibitor therapy: 105 (19.6%) olaparib patients vs 123 (45.7%) placebo patients. |
| OSHRD-positive population | exploratoryRay-Coquard 2023 | 65.5% at 5 y | 48.4% at 5 y | HR 0.62 (95% CI 0.45–0.85)Prespecified exploratory analysis by biomarker status; the authors call the improvement clinically meaningful. |
| PFSHRD-positive population | long term-updateRay-Coquard 2023 | 46.1% at 5 y | 19.2% at 5 y | HR 0.41 (95% CI 0.32–0.54)Updated PFS at 5 years in the exploratory HRD-positive population. |
| Endpoint | Analysis | Olaparib plus bevacizumab | Placebo plus bevacizumab | Effect |
|---|---|---|---|---|
| PFSRandomised patients (N=806); analysis population not stated in the abstract | primarymedian follow-up 22.9 monthsRay-Coquard 2019 | median 22.1 months | median 16.6 months | HR 0.59 (95% CI 0.49–0.72)P<0.001Investigator-assessed. |
| PFSHRD-positive tumours, including those with BRCA mutations | exploratorymedian follow-up 22.9 monthsRay-Coquard 2019 | median 37.2 months | median 17.7 months | HR 0.33 (95% CI 0.25–0.45)The 2023 report describes the biomarker analyses as prespecified and exploratory. |
| PFSHRD-positive tumours without a BRCA mutation | exploratorymedian follow-up 22.9 monthsRay-Coquard 2019 | median 28.1 months | median 16.6 months | HR 0.43 (95% CI 0.28–0.66)Exploratory subgroup. |
| OS | finalRay-Coquard 2023 | median 56.5 months | median 51.6 months | HR 0.92 (95% CI 0.76–1.12)P=0.4118Median follow-up 61.7 months (olaparib) and 61.9 months (placebo). Subsequent PARP inhibitor therapy: 105 (19.6%) olaparib patients vs 123 (45.7%) placebo patients. |
| OSHRD-positive population | exploratoryRay-Coquard 2023 | 65.5% at 5 y | 48.4% at 5 y | HR 0.62 (95% CI 0.45–0.85)Prespecified exploratory analysis by biomarker status; the authors call the improvement clinically meaningful. |
| PFSHRD-positive population | long term-updateRay-Coquard 2023 | 46.1% at 5 y | 19.2% at 5 y | HR 0.41 (95% CI 0.32–0.54)Updated PFS at 5 years in the exploratory HRD-positive population. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.59 | 0.49–0.72 |
| PFS | 0.33 | 0.25–0.45 |
| PFS | 0.43 | 0.28–0.66 |
| OS | 0.92 | 0.76–1.12 |
| OS | 0.62 | 0.45–0.85 |
| PFS | 0.41 | 0.32–0.54 |
- Olaparib plus bevacizumab (experimental)
- Placebo plus bevacizumab (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 bevacizumab | Placebo plus bevacizumab |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 14 | 64.5% | 55.7% |
| 28 | 41.6% | 31.1% |
| 41 | 27.6% | 18.1% |
| 55 | 17.8% | 10.1% |
- Olaparib plus bevacizumab (experimental)
- Placebo plus bevacizumab (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 bevacizumab | Placebo plus bevacizumab |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 23 | 65.1% | 40.6% |
| 47 | 41.7% | 15.9% |
| 70 | 27.1% | 6.4% |
| 93 | 17.7% | 2.6% |
Appears in
Sources
Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, et al. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019;381(25):2416-2428.
Ray-Coquard I, Leary A, Pignata S, Cropet C, González-Martín A, Marth C, et al. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023;34(8):681-692.