Cediranib may improve response rates in non-small-cell lung cancer

NEW YORK (Reuters Health) - Adding cediranib to carboplatin/paclitaxel may improve response rates and progression-free survival in advanced non-small-cell lung cancer (NSCLC), but toxicity is significant at the 30-mg daily dose, new research shows.

Cediranib was previously shown in phase 1 and 2 trials to have encouraging tumor control and to be tolerated at a daily dose of 45 mg, lead author Dr. Glenwood D. Goss from The Ottawa Hospital Cancer Centre, Canada and colleagues note in the November 16th Journal of Clinical Oncology.

The researchers initiated the current phase 2/3 trial in advanced NSCLC to test cediranib in combination with carboplatin/paclitaxel, but the dose was reduced from 45 to 30 mg after a toxicity-related death occurred in the cediranib arm.

Enrollment was then limited to patients with good performance status, and the study did not proceed to phase 3.

Among patients in the 30-mg cohort, median progression-free survival was 5.6 months for cediranib and 5 months for placebo (P=0.13), the authors report, but the difference approached significance after adjustment for predefined baseline factors (P=0.08).

The complete and partial response rate was 38% (duration, 4.4 months) for cediranib and 16% for placebo. In multivariate analyses, cediranib and performance status were predictive of response.

Among patients in the 45-mg cohort, the response rate was 50% for cediranib and 35% for placebo, and a clear dose relationship was seen for toxicity and dose intensity.

Cediranib patients were more likely than placebo patients to experience adverse events, including serious adverse events from any cause within 30 days of the last dose of study drug.

Causes of death for the 9 cediranib patients for whom protocol toxicity was considered to have been at least in part causal were disparate with no clear pattern of toxicity.

"Although concerns regarding tolerability and dose intensity precluded immediate progression to phase 3 testing, the study did meet its predefined efficacy end point to proceed to phase 3 testing," the investigators say.

"Although we did not formally study cediranib 20 mg as a starting dose in combination with paclitaxel/carboplatin, 37% of patients on our study required dose modification to 20 mg," the researchers note. "Exploratory analyses comparing 45 mg versus 20 mg cycles confirmed a clear dose and toxicity relationship."

"Based on these data," the authors conclude, "NCIC CTG and the Australasian Lung Cancer Trials Group have initiated a prospective, randomized, double-blind, placebo-controlled trial of cediranib (20 mg) with carboplatin and paclitaxel in stage IIIB and IV NSCLC."

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