Source: DGNews  |  Posted 2 years ago

By Chris Berrie

BARCELONA, Spain -- December 1, 2009 -- Cediranib is safe and well tolerated,
and shows significant antitumour activity compared with placebo in patients
with advanced renal cell carcinoma (RCC), according to research presented at
the 2nd European Multidisciplinary Meeting on Urological Cancers (EMUC).

Principal investigator Peter Mulders, MD, PhD, University Medical Centre St
Radboud, Nijmegen, Netherlands, led a randomised, double-blind, parallel-group,
phase 2 study to compare safety and efficacy of cediranib versus placebo in
patients with advanced RCC. He presented the results here on November 29.

The entry criteria included metastatic or recurrent clear-cell
RCC/adenocarcinoma, with a World Health Organization performance status (WHO
PS) of 0 to 2. Individuals were excluded who had received previous
anti-vascular endothelial growth factor therapy, more than 1 previous
immunotherapy, or prior chemotherapy (except 5-fluorouracil with immunotherapy).

Seventy-one patients were initially randomised 1:3 to placebo (n = 18; male,
83%) or cediranib 45 mg (n = 53; male 75%).

“After 12 weeks,” Dr. Mulders explained, “the study treatment was unblinded
and, in the case where placebo showed progression, there was crossover to the
cediranib treatment.”

Baseline characteristics across these treatment groups were well balanced, with
patients mainly under the age of 75 years (95% vs 96%), with a WHO PS of 0/1
(95% vs 97%), and a clear-cell histology (83% vs 91%), with about 50% having
undergone immunotherapy/hormonal therapy, and almost all following surgery (89%
vs 92%).

The primary objective was efficacy of cediranib as determined by changes from
baseline in tumour size to 12 weeks of therapy. Secondary objectives included
response rate and duration according to the Response Evaluation Criteria in
Solid Tumours criteria, progression-free survival (PFS), and safety and
tolerability.

After the 12 weeks of treatment, cediranib showed significant benefit over
placebo for change in tumour size: -20% versus +19% (P < .0001).
With a response rate (all partial responders) of 34% and 47% with stable
disease, the overall disease control rate was 81%.

For median PFS, cediranib showed significant prolongation over placebo (12.1 vs
2.8 months; hazard ratio [HR], 0.45; 90% confidence interval [CI], 0.26-0.76;
P = .017). In an exploratory analysis, where this was also corrected
for confounding effects of patient crossover from placebo to cediranib, the HR
was 0.14 (90% CI, 0.06-0.30; P < .0001).

The most frequently reported adverse events with cediranib were all-grade
diarrhoea (88%), fatigue (66%), hypertension (61%), and dysphonia (63%). Of
note, 87% of patients treated with cediranib at some point during the study had
a dose reduction or treatment pause. Dr. Mulders noted that the overall mean
daily dose of cediranib, therefore, was approximately 30 mg.

EMUC was jointly organised by the European Association of Urology (EAU), the
European Society for Medical Oncology (ESMO), and the European Society for
Therapeutic Radiology and Oncology (ESTRO).

Presentation title: Cediranib (Recentin) in Patients With Advanced Renal
Cell Carcinoma (RCC): Final Results of a Phase II Randomised Study. Oral
Abstract O6