Addition of Cediranib to Carboplatin/Paclitaxel Improves Progression-Free Survival in Metastatic/Recurrent Cervical Cancer in UK Phase II Trial
In a UK phase II trial reported in The Lancet Oncology, Symonds et al found that the addition of the investigational VEGFR1, -2, and -3 inhibitor cediranib to carboplatin/paclitaxel improved progression-free survival in patients with metastatic or relapsed cervical cancer. The addition of cediranib was also associated with greater toxicity.
Study Details
In the double-blind trial, 69 patients from 17 UK centers were randomly assigned between August 2010 and July 2012 to receive carboplatin/paclitaxel plus oral cediranib at 20 mg (n = 34) or placebo (n = 35) once daily until disease progression. Women were initially diagnosed with metastatic carcinoma or developed metastatic disease or local pelvic recurrence after radical treatment.
Carboplatin was given at an area under the concentration-time curve [AUC] of 5 and paclitaxel at 175 mg/m² every 3 weeks for a maximum of six cycles. The primary endpoint was progression-free survival.
Progression-Free Survival
Median follow-up was 24.2 months. Median progression-free survival was 8.1 months (80% confidence interval [CI] = 7.4–8.8 months) in the cediranib group vs 6.7 months (80% CI = 6.2–7.2 months) in the placebo group (hazard ratio [HR] = 0.58, 80% CI = 0.40–0.85, one-sided P = .032).
Adverse Events
The most common grade ≥ 3 adverse events in the cediranib group were neutropenia (31% vs 11%), febrile neutropenia (16% vs 0%), diarrhea (16% vs 3%), leukopenia (16% vs 9%), and fatigue (13% vs 6%). Grade 2 or 3 hypertension was more common with cediranib (34% vs 11%). Serious adverse events occurred in 59% vs 51% of patients.
The investigators concluded: “Cediranib has significant efficacy when added to carboplatin and paclitaxel in the treatment of metastatic or recurrent cervical cancer. This finding was accompanied by an increase in toxic effects (mainly diarrhea, hypertension, and febrile neutropenia).”
R. Paul Symonds, FRCR, of University of Leicester, is the corresponding author for the Lancet Oncology article.
The study was funded by Cancer Research UK and AstraZeneca. For full disclosures of the study authors, visit www.thelanet.com/journals/lanonc/.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
