Wild-type KRAS Colorectal Tumours Respond To Panitumumab

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Main Category: Colorectal Cancer
Also Included In: GastroIntestinal / Gastroenterology;  Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 01 Feb 2008 - 10:00 PDT

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Patients with colorectal tumours expressing the wild-type KRAS gene show significantly increased progression free survival with panitumumab (Vectibix), a monoclonal antibody targeting EGFR, while those with mutations in KRAS do not, according to data from a phase 3 trial reported at the 2008 Gastrointestinal Cancers Symposium this week (25-27 January, Orlando, Florida).

The study assessed KRAS status - a gene coding for a protein involved in signalling cell division - in tumour samples from 427 patients with metastatic colorectal cancer taking part in a phase 3 trial in which they were randomised to panitumumab (6.0mg/kg every two weeks) plus best supportive care or best supportive care alone. Results reported at the meeting showed that 43% of these patients had KRAS mutations.

Patients with tumours expressing wild-type KRAS showed a 55% increase in progression free survival when treated with panitumumab compared to those given best supportive care without the antibody (hazard ratio 0.45; 95% confidence interval 0.34-0.59). In contrast, those with mutant KRAS showed no response (HR 0.99; 95% CI, 0.73-1.36) (p<0.0001). The median progression free survival was significantly longer, at 12.3 weeks, in patients with wild type KRAS treated with panitumumab than those with mutant KRAS (7.4 weeks). This compared with 7.3 weeks in both KRAS groups treated with best supportive care.

In the group of patients treated with panitumumab, 17% of those with wild type KRAS expressing tumours responded and 34% had stable disease, while 0% of those with mutant KRAS responded and 12% had stable disease.

Reporting the results, Rafael Amado, executive director, oncology, Amgen Inc, Thousand Oaks, California, USA, said: "In patients with chemotherapy-refractory metastatic colorectal cancer, the clinical efficacy of panitumumab monotherapy appears to be restricted to patients with wild type KRAS tumours." He added: "KRAS genotyping of tumours should be strongly considered in patients being treated with panitumumab monotherapy."

Panitumumab is currently approved in Europe as monotherapy for the treatment of patients with EGFR expressing metastatic colorectal carcinoma with non-mutated (wild-type) KRAS, and after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

[2008 Gastrointestinal Cancers Symposium. Abstract 278]

http://www.amgen.com

Written by - Susan Mayor PhD, medical journalist, London, UK
susanmayor@mac.com
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