| General information |
| Database: | DB00512 |
| Objective: | The aim of this study was to assess the efficacy and tolerability of olaparib in combination with chemotherapy, followed by olaparib maintenance monotherapy, versus chemotherapy alone in patients with platinumsensitive, recurrent, highgrade serous ovarian cancer. |
| Authors: | Oza AM, et al |
| Title: | Olaparib combined with chemotherapy for recurrent platinumsensitive ovarian cancer: a randomisedphase 2 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 25481791 |
| Trial Design |
| Clinical Trial Id: | NCT01081951 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | ovarian cancer |
| Cancer Subtype: | ovarian cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Olaparib combined with chemotherapy |
| Study Type: | multicentre, multinationalphase II, openlabelstudy |
| Key Patients Feature: | Eligible participants were aged 18 years or olderand had histologically or cytologically diagnosed ovarian cancer, including primary peritoneal and fallopian tubecancer, with serous histology or a serous component.Patients had received a maximum of three previouscourses of platinumbased chemotherapy and, in theinvestigator¡¯s opinion, were progression free for at least6 months before randomisation. Other key eligibilitycriteria included: at least one measurable lesion; EasternCooperative Oncology Group (ECOG) performancestatus of 0, 1, or 2; and adequate bone marrow, hepatic, and renal function |
| Biomarker: | BRCA mutation status |
| Biomark Analysis: | progression free survival was significantly longer in the olaparib plus chemotherapy group (median 12.2 months [95% CI 9.715.0]) than in the chemotherapy alone group (median 9.6 months [95% CI 9.19.7) (HR 0.51 [95% CI 0.340.77]; p=0.0012), especially in patients with BRCA mutations (HR 0.21 [0.080.55] |
| Control Group Info: | single arm |
| Treatment Info: | pts received either olaparib (200 mg capsules twice daily, administered orally on days 110 of each 21day cycle) plus paclitaxel (175 mg/m(2), administered intravenously on day 1) and carboplatin (area under the curve [AUC] 4 mg/mL per min, according to the Calvert formula, administered intravenously on day 1), then olaparib monotherapy (400 mg capsules twice daily, given continuously) until progression (the olaparib plus chemotherapy group), or paclitaxel (175 mg/m(2) on day 1) and carboplatin (AUC 6 mg/mL per min on day 1) then no further treatment (the chemotherapy alone group). |
| Primary End Point: | progression free survival |
| Secondary End Point: | NA |
| Patients Number: | 173 |
| Trial Results |
| DLT_MTD: | In the combinationphase, adverse events that were reported at least 10% more frequently with olaparib plus chemotherapy than with chemotherapy alone were alopecia (60 [74%] of 81 vs 44 [59%] of 75), nausea (56 [69%] vs 43 [57%]), neutropenia (40 [49%] vs 29 [39%]), diarrhoea (34 [42%] vs 20 [27%]), headache (27 [33%] vs seven [9%]), peripheral neuropathy (25 [31%] vs 14 [19%]), and dyspepsia (21 [26%] vs 9 [12%]); most were of mildtomoderate intensity. The most common grade 3 or higher adverse events during the combinationphase were neutropenia (in 35 [43%] of 81 patients in the olaparib plus chemotherapy group vs 26 [35%] of 75 in the chemotherapy alone group) and anaemia (seven [9%] vs five [7%]). Serious adverse events were reported in 12 (15%) of 81 patients in the olaparib plus chemotherapy group and 16 of 75 (21%) patients in the chemotherapy alone group. |
| Objective Response Rate: | in Olaparib plus chemotherapy (n=81), Complete response 10%, Partial response 54%, Overall response 64%. Chemotherapy alone (n=81), Complete response 7%, Partial response 51%, Overall response 58%. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | progression free survival was significantly longer in the olaparib plus chemotherapy group (median 12.2 months [95% CI 9.7-15.0]) than in the chemotherapy alone group (median 9.6 months [95% CI 9.1-9.7) (HR 0.51 [95% CI 0.34-0.77]; p=0.0012), especially in patients with BRCA mutations (HR 0.21 [0.08-0.55]; p=0.0015). |
| Median OS A vs. C: | 33.8 months(95% CI 26.9-38.5) in combined arm, 37.6 months(95% CI 27.8-44.6) in monotherapy arm. |
| Adverse Event(agent arm): | In the combinationphase, adverse events that were reported at least 10% more frequently with olaparib plus chemotherapy than with chemotherapy alone were alopecia (60 [74%] of 81 vs 44 [59%] of 75), nausea (56 [69%] vs 43 [57%]), neutropenia (40 [49%] vs 29 [39%]), diarrhoea (34 [42%] vs 20 [27%]), headache (27 [33%] vs seven [9%]), peripheral neuropathy (25 [31%] vs 14 [19%]), and dyspepsia (21 [26%] vs 9 [12%]); most were of mildtomoderate intensity. The most common grade 3 or higher adverse events during the combinationphase were neutropenia (in 35 [43%] of 81 patients in the olaparib plus chemotherapy group vs 26 [35%] of 75 in the chemotherapy alone group) and anaemia (seven [9%] vs five [7%]). Serious adverse events were reported in 12 (15%) of 81 patients in the olaparib plus chemotherapy group and 16 of 75 (21%) patients in the chemotherapy alone group. |
| Conclusions: | Olaparib plus paclitaxel and carboplatin followed by maintenance monotherapy significantly improved progression free survival versus paclitaxel plus carboplatin alone, with the greatest clinical benefit in BRCAmutated patients, and had an acceptable and manageable tolerability profile. |