| General information |
| Database: | DB00514 |
| Objective: | They investigated whether this combination could improve progression free survival (PFS) compared with olaparib monotherapy in women with recurrent platinumsensitive ovarian cancer. |
| Authors: | Liu JF, et al |
| Title: | Combination cediranib and olaparib versus olaparib alone for women with recurrent platinumsensitive ovarian cancer: a randomisedphase 2 study. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 25218906 |
| Trial Design |
| Clinical Trial Id: | NCT01116648 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | ovarian, primary peritoneal, or fallopian tube carcinoma |
| Cancer Subtype: | epithelial ovarian, primary peritoneal, or fallopian tube carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | Combination cediranib and olaparib |
| Study Type: | randomized, openlabel, phase II trial |
| Key Patients Feature: | Eligibility criteria included age more than and equal to 18 years, ECOG performance status 0 or 1, estimated lifeexpectancy >6 months, and recurrent highgrade serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer. gBRCAm patients with any highgradehistology were considered eligible. patients were required to have platinumsensitivedisease, defined as disease recurrence >6 months after the last receipt of platinum and noevidence of progression on a prior platinumcontaining regimen. Patients could havereceived an unlimited number of prior platinumbased chemotherapies, but no more than onenonplatinum therapy in the recurrent setting. patients were also required to have measurabledisease by RECIST 1.1 criteria. Prior antiangiogenic agents were permitted only in the frontline (including maintenance) setting. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Combination cediranib and olaparib versus olaparib alone |
| Treatment Info: | They randomly allocated participants (1:1) according to permuted blocks, stratified by germline BRCA status and previous antiangiogenic therapy, to receive olaparib capsules 400 mg twice daily or the combination at the recommendedphase 2 dose of cediranib 30 mg daily and olaparib capsules 200 mg twice daily. |
| Primary End Point: | progression free survival |
| Secondary End Point: | NA |
| Patients Number: | 90 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Best overall responses on single agent olaparib included 2 complete responses (CR), 20 partial responses (PR), 19 stable disease (SD), and 1 progressive disease (PD). Responses on the combination arm included 5 CR, 30 PR, 8 SD, and no primary progression events. Six CRs occurred in gBRCAm women; 1 CR occurred in a gBRCAwt woman on the combination arm. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was significantly longer with cediranib/olaparib (17.7 vs. 9.0 mos, HR 0.42; p = 0.005). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade 3 and 4 adverse events were more common with cediranib/olaparib, including fatigue (12 vs. 5), diarrhea (10 vs. 0), and hypertension (18 vs. 0). |
| Conclusions: | Cediranib plus olaparib seems to improve PFS in women with recurrent platinumsensitive highgrade serous or endometrioid ovarian cancer, and warrants study in aphase 3 trial. The sideeffect profile suggests such investigations should include assessments of quality of life and patientreported outcomes to understand the effects of a continuing oral regimen with that of intermittent chemotherapy. |