Study 19
Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer
Phase 2N = 265NCT00753545
- Population
- Platinum-sensitive relapsed high-grade serous ovarian cancer after two or more platinum-based regimens, in response to the latest; BRCA mutation status was not a selection criterion (136 patients had a deleterious BRCA mutation in the updated survival analysis)
- Design
- Randomised, double-blind, placebo-controlled phase 2 study. Patients with platinum-sensitive relapsed high-grade serous ovarian cancer who had received two or more platinum-based regimens and had a partial or complete response to the most recent one received olaparib 400 mg twice daily (capsules) or placebo. Primary end point PFS per RECIST.
- Primary endpoint
- PFS
- Arms
- Olaparib capsules (experimental, n = 136): Olaparib 400 mg twice daily (capsules)
- Placebo (control, n = 129): Matching placebo
- People
- Ledermann J
PFSHR 0.35 (95% CI 0.25–0.49)Δ median PFS+3.6 monthsOSHR 0.94 (95% CI 0.63–1.39)OSHR 0.73 (95% CI 0.55–0.96)Δ median OS+2 monthsOSHR 0.62 (95% CI 0.41–0.94)
Show the numbers
| Endpoint | Analysis | Olaparib capsules | Placebo | Effect |
|---|---|---|---|---|
| PFSRandomised patients (N=265); analysis population not stated in the abstract | primaryLedermann 2012 | median 8.4 months | median 4.8 months | HR 0.35 (95% CI 0.25–0.49)P<0.001Medians are counted from randomization on completion of chemotherapy. Primary end point: PFS per RECIST. |
| OSRandomised patients (N=265); analysis population not stated in the abstract | interimLedermann 2012 | — | — | HR 0.94 (95% CI 0.63–1.39)P=0.75Interim analysis at 38% data maturity; the abstract reports no significant difference. |
| OS | long term-updateLedermann 2016 | median 29.8 months (26.9–35.7) | median 27.8 months (24.9–33.7) | HR 0.73 (95% CI 0.55–0.96)P=0.025 (nominal)Descriptive analysis at 77% data maturity (secondary end point; the study was not powered for OS). The nominal p=0.025 did not meet the required threshold for statistical significance of p<0.0095. |
| OSDeleterious BRCA mutation subgroup (n=136) | exploratoryLedermann 2016 | median 34.9 months (29.2–54.6) | median 30.2 months (23.1–40.7) | HR 0.62 (95% CI 0.41–0.94)P=0.025 (nominal)Subgroup analysis; 136 patients had a deleterious BRCA mutation. BRCA wild-type subgroup: HR 0.83 (95% CI 0.55-1.24), nominal p=0.37. |
| Endpoint | Analysis | Olaparib capsules | Placebo | Effect |
|---|---|---|---|---|
| PFSRandomised patients (N=265); analysis population not stated in the abstract | primaryLedermann 2012 | median 8.4 months | median 4.8 months | HR 0.35 (95% CI 0.25–0.49)P<0.001Medians are counted from randomization on completion of chemotherapy. Primary end point: PFS per RECIST. |
| OSRandomised patients (N=265); analysis population not stated in the abstract | interimLedermann 2012 | — | — | HR 0.94 (95% CI 0.63–1.39)P=0.75Interim analysis at 38% data maturity; the abstract reports no significant difference. |
| OS | long term-updateLedermann 2016 | median 29.8 months (26.9–35.7) | median 27.8 months (24.9–33.7) | HR 0.73 (95% CI 0.55–0.96)P=0.025 (nominal)Descriptive analysis at 77% data maturity (secondary end point; the study was not powered for OS). The nominal p=0.025 did not meet the required threshold for statistical significance of p<0.0095. |
| OSDeleterious BRCA mutation subgroup (n=136) | exploratoryLedermann 2016 | median 34.9 months (29.2–54.6) | median 30.2 months (23.1–40.7) | HR 0.62 (95% CI 0.41–0.94)P=0.025 (nominal)Subgroup analysis; 136 patients had a deleterious BRCA mutation. BRCA wild-type subgroup: HR 0.83 (95% CI 0.55-1.24), nominal p=0.37. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.35 | 0.25–0.49 |
| OS | 0.94 | 0.63–1.39 |
| OS | 0.73 | 0.55–0.96 |
| OS | 0.62 | 0.41–0.94 |
- Olaparib capsules (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 | Olaparib capsules | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 5 | 66.2% | 48.6% |
| 11 | 40.3% | 20.4% |
| 16 | 26.7% | 9.9% |
| 21 | 17.7% | 4.8% |
- Olaparib capsules (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 | Olaparib capsules | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 19 | 64.3% | 62.3% |
| 37 | 42.3% | 39.8% |
| 56 | 27.2% | 24.8% |
| 75 | 17.5% | 15.4% |
Appears in
Sources
Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382-92.
Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016;17(11):1579-1589.