Latest Erbitux Data On Metastatic Colorectal Cancer Presented At WCGIC Underline Benefits In Patients With KRAS Wild-Type Tumors

Main Category: Colorectal Cancer
Also Included In: GastroIntestinal / Gastroenterology;  Cancer / Oncology
Article Date: 25 Jun 2009 - 4:00 PDT

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Latest Erbitux® (cetuximab) data presented today at the World Congress on Gastrointestinal Cancer (WCGIC) reinforce the value of the targeted therapy in the treatment of metastatic colorectal cancer (mCRC) patients with KRAS wild-type (wt) tumors. Results from the CRYSTALa and CELIMb trials have provided further evidence that KRAS mutation status is the current accepted standard predictive biomarker for Erbitux efficacy in patients with mCRC. In addition, new data have shown that the rash associated with Erbitux therapy can be effectively treated with a cream containing vitamin K.

"The data presented at WCGIC today are a potent reminder of the significant efficacy demonstrated by Erbitux in the treatment of metastatic colorectal cancer and of the unique role it plays in the personalized treatment of patients with KRAS wild-type tumors, all of which underscores the need for every patient to be tested for KRAS status at diagnosis," said Dr Wolfgang Wein, Executive Vice President, Oncology, Merck Serono. "Moreover, this new evidence shows that the rash associated with EGFR-targeted agents can be effectively and economically treated, thereby further improving the already favorable tolerability of this therapy."

CRYSTAL: Erbitux personalizes cancer care by significantly improving response rates (RR) and progression-free survival (PFS) in patients with KRAS wild-type tumors

Latest results from the multicenter, Phase III, randomized, controlled CRYSTAL trial demonstrate that the addition of Erbitux to the standard FOLFIRI chemotherapy regimen resulted in a significantly improved RR (59.3% vs. 43.2%, p=0.003) and PFS (9.9 vs. 8.7 months; Hazard Ratio (HR)=0.68; p=0.017) compared to FOLFIRI alone in mCRC patients with KRAS wt tumors.

BRAF is located 'downstream' of KRAS in the EGFR signaling pathway targeted by Erbitux and a retrospective analysis was conducted to determine whether BRAF mutation status also plays a role in influencing Erbitux efficacy in mCRC patients. BRAF mutation was found to have occurred in only 5% of the BRAF-evaluable population (529 patients),3 and therefore the clinical utility of this potential biomarker may be limited. KRAS is therefore currently the only predictive biomarker in the treatment of mCRC for which there is meaningful clinical evidence.

CELIM: High response rate seen with Erbitux results in significantly improved resectability rates and greater potential for cure in patients with KRAS wild-type tumors

Complete resection (R0) of liver metastases provides mCRC patients with the only possibility of a cure from the disease. Non-resectable metastases may become resectable following effective treatment with chemotherapy, or chemotherapy plus Erbitux.

Updated results from the CELIM study presented at WCGIC demonstrate that the combination of Erbitux with chemotherapy resulted in a high RR in patients with KRAS wt mCRC (70%). In a new analysis, a group of seven surgeons retrospectively conducted an independent, objective review of scans from 75 patients included in the CELIM study. Resectability according to the scans increased significantly during the study from 32% prior to the Erbitux treatment combination to 60% after treatment (p<0.01).

Rapidly efficacious treatment for rash associated with Erbitux use

Preclinical evidence suggested that topically-applied vitamin K can reactivate EGFR signaling in the skin after systemic administration of EGFR-targeted anti-cancer agents. In an independent study run at the Institute of Oncology in Ljubljana, Slovenia, 79 patients with mCRC who were receiving weekly Erbitux in addition to chemotherapy were monitored for rash. The 69 (87%) patients who developed the rash received twice-daily topical treatment with a cream containing urea and 0.1% vitamin K1. Application of the cream produced noticeable improvement within a median of 1.2 weeks, with a reduction in the severity of the rash of at least one grade seen within a median of 2.3 weeks. Importantly, only 7% of patients in this study required an Erbitux dose reduction due to rash, confirming the efficacy of the cream.1

More than 413,000 people develop colorectal cancer in Europe every year, accounting for 13% of the total cancer burden and around 200,000 deaths. Approximately 25% of patients present with metastatic disease, and 5-year survival rates for patients with mCRC can be as low as 5%.

aCRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer

bCELIM: Randomized multicenter study of CEtuximab plus FOLFOX or FOLFIRI in neoadjuvant treatment of non-resectable colorectal LIver Metastases

Source
Merck Serono

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