Studies Demonstrate Increased Efficacy Of Erbitux In Metastatic Colorectal Cancer Patients With KRAS Wild-type Tumors

Findings from three studies demonstrate the increased efficacy of Erbitux® (cetuximab) in patients with metastatic colorectal cancer (mCRC) who have a wild-type KRAS tumor, highlighting the potential role of KRAS as a predictive biomarker in the treatment of this common cancer.1-3

Data presented at the American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium in Orlando, FL, showed that response rate (RR) for Erbitux plus FOLFIRI was higher for the patient population with wild-type KRAS than for those patients with mutated KRAS. The wild-type KRAS patients showed a RR of 55% versus 32% for those with mutated KRAS. The relative risk of progression in the KRAS wild-type group was reduced by 53% compared to the KRAS mutant group.

Two other retrospectively analyzed studies recently published in the Journal of Clinical Oncology and Annals of Oncology confirm this clinically important correlation.

"Biomarkers are proving to be an interesting area of investigation. Not only do the results demonstrate that Erbitux is highly effective in patients with KRAS wild-type tumors but they also add to the pool of evidence that supports the use of predictive factors in the future of oncology treatment," commented study principal investigator, Professor Josep Tabernero, Vall D'Hebron University Hospital, Barcelona, Spain. "These data give the first evidence of the importance of KRAS as a biomarker in the first-line setting as well as in pretreated patients. Using biomarkers to predict which patients are likely to respond best to targeted therapies allows us to stratify their treatment appropriately and thus improve outcomes. This is of particular importance in the first-line setting as it enables us to select the best treatment strategy for the patient with metastatic disease from day one."

The wild-type or non-mutant KRAS gene is found in up to 65% of colorectal cancer patients and it may prove to be an important biomarker for predicting patient response to targeted treatments such as Erbitux that inhibit the epidermal growth factor receptor (EGFR) pathway.

The two retrospective analyses investigating the impact of KRAS mutations on the efficacy of Erbitux demonstrated that patients with mCRC who have the wild-type KRAS tumor realize a greater benefit from Erbitux in combination with irinotecan-based chemotherapy than those patients with a KRAS mutation.1,2

- The study recently published in the Journal of Clinical Oncology found that pretreated mCRC patients with KRAS wild-type tumors had improved survival over patients with a mutated KRAS tumor [median PFS: 31 weeks vs 10 weeks, p=0.0001].2

- The second study published in Annals of Oncology also demonstrated an improved survival in pretreated mCRC patients with KRAS wild-type tumors vs. tumors with the mutated gene [median overall survival (OS): 43 weeks vs. 27 weeks respectively, p=0.020]. In addition, the results found that patients with the wild-type tumor experienced more significant decreases in tumor size than patients with a mutated tumor, and these patients experienced significantly better OS compared to those without decreases in tumor size [median OS: 75 weeks vs 31 weeks, p=0.00000012].1

"The treatment outcome with Erbitux in combination with irinotecan for metastatic CRC patients with KRAS wild-type tumors reported in these analyses is outstanding for a population of pretreated patients. Progression free survival clearly exceeds earlier findings in non-selected patients," said Professor Pierre Laurent-Puig from the Université Paris-Descartes and Assistance Publique-Hôpitaux de Paris, France.

"These studies demonstrate - in both first-line and pretreated settings - the consistent, clinically relevant efficacy of Erbitux in metastatic CRC patients with KRAS wild-type tumors, further exceeding the benefit provided by Erbitux plus irinotecan in non-selected patients," added Professor Sabine Tejpar, University Hospital Gasthuisberg in Leuven, Belgium.

Merck Serono is committed to improving the lives of people with cancer and is pioneering research into the use of biomarkers to identify patients who will most benefit from treatment with targeted therapies such as Erbitux. The ongoing analyses of the large randomized first-line studies of Erbitux in combination with chemotherapy will further help to understand the potential role of KRAS in the treatment of metastatic colorectal cancer.

More than 370,000 people develop colorectal cancer in Europe every year, accounting for 13% of the total cancer burden and around 200,000 deaths.4 Approximately 25% of patients present with metastatic disease.5 Five-year survival rates for patients with mCRC are as low as 5%.6