Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial
| Autor: | Laura Farrelly, Mahesh K.B. Parmar, Gordon J. S. Rustin, Richard Kaplan, Ann Marie Swart, Elizabeth Eisenhauer, Stan B. Kaye, Fharat A. Raja, Michael Friedlander, Dan Stark, Hal W. Hirte, Elizabeth Clark, Timothy J. Perren, Adrian Cook, Jonathan A. Ledermann, Andrew C. Embleton, Gordon C Jayson, Antonio González-Martín, Michelle D. Vaughan |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Carcinoma Ovarian Epithelial Placebo Carboplatin law.invention Cediranib 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Double-Blind Method Randomized controlled trial law Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Neoplasms Glandular and Epithelial Prospective Studies Aged Medicine(all) Ovarian Neoplasms Intention-to-treat analysis business.industry Cancer General Medicine Middle Aged medicine.disease Surgery Clinical trial Treatment Outcome 030104 developmental biology chemistry 030220 oncology & carcinogenesis Quinazolines Female Neoplasm Recurrence Local business Ovarian cancer medicine.drug |
| Popis: | SummaryBackgroundAngiogenesis is a validated clinical target in advanced epithelial ovarian cancer. Cediranib is an oral antiangiogenic vascular endothelial growth factor receptor 1–3 inhibitor that has shown antitumour activity in recurrent ovarian cancer. We assessed efficacy and safety of cediranib in combination with platinum-based chemotherapy and as continued maintenance treatment in patients with first relapse of platinum-sensitive ovarian cancer.MethodsIn this randomised, three-arm, double-blind, placebo-controlled phase 3 trial, we randomly assigned patients aged 18 years or older with relapsed platinum-sensitive ovarian cancer at 63 centres in Australia, Canada, New Zealand, Spain, and the UK. Participants received up to six cycles of platinum-based chemotherapy (once every 3 weeks) then entered a maintenance phase. Participants were randomly allocated (2:3:3), with five stratification factors and in alternating blocks, to receive placebo alongside chemotherapy and then placebo only maintenance (arm A; reference), cediranib 20 mg once-daily alongside chemotherapy then placebo only maintenance (arm B; concurrent), or cediranib 20 mg once-daily alongside chemotherapy then cediranib 20 mg once-daily maintenance (arm C; maintenance). Patients continued treatment to progression or excessive toxic effects. The primary efficacy endpoint was progression-free survival between arms A and C. Efficacy analysis was by intention to treat. Safety was assessed in all patients who received the allocated study drug. This trial is registered with ClinicalTrials.gov, number NCT00532194; the ISRCTN registry, number ISRCTN68510403; and ANZ Clinical Trials Registry, number ACTRN1261000016003.FindingsWe randomly assigned 486 women between Nov 13, 2007, and Dec 23, 2011; results presented are for 456 patients randomly assigned subsequent to the 30mg safety phase. During a median of 19·5 months (IQR 14–26) follow-up, 113 (96%) of 118 women assigned to arm A and 141 (86%) of 164 assigned to arm C had disease progression. Median progression-free survival was 11·0 months (95% CI 10·4–11·7) in arm C and 8·7 months (7·7–9·4) in arm A (hazard ratio 0·56, 0·44–0·72, p |
| Databáze: | OpenAIRE |
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