Erbitux® (cetuximab) Combined With Chemotherapy Extends Survival From 21 To Nearly 25 Months For KRAS Wild-Type Metastatic Colorectal Cancer Patie

Main Category: Colorectal Cancer
Also Included In: GastroIntestinal / Gastroenterology;  Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 19 Sep 2008 - 5:00 PDT

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Merck Serono today announced the overall survival data from the phase III CRYSTAL* trial, which found that patients with KRAS wild-type tumours treated with Erbitux® (cetuximab) in combination with chemotherapy experienced a median overall survival of nearly 25 months - the first time median survival in metastatic colorectal cancer (mCRC) has exceeded two years in a randomised phase III trial.

The results, presented today at the 33rd European Society for Medical Oncology (ESMO) congress, demonstrated that patients with KRAS wild-type tumours receiving cetuximab plus chemotherapy (FOLFIRI) experienced an overall survival of 24.9 months (n=172), compared with 21.0 months in patients receiving chemotherapy (FOLFIRI) alone (n=176) - nearly a four month increase in survival (HR: 0.84; p=0.22).1 Overall survival in patients with KRAS mutant tumours did not differ between the treatment arms (17.5 months versus 17.7 months respectively (HR=1.03, p=0.85)).1

"This is a very exciting step forward in targeted cancer therapy," commented Professor Tim Maughan, Honorary Consultant Clinical Oncologist at Velindre Hospital, Cardiff and Professor of Cancer Studies at Cardiff University. "By selecting individuals who stand to benefit most from cetuximab - those with KRAS wild-type tumours - the median survival of patients in the CRYSTAL study has exceeded 24 months in the cetuximab arm. This has not been achieved before in a Phase III trial of patients with metastatic colorectal cancer."

Today's announcement follows news in July of the European Commission's approval for cetuximab to extend its licence to the 1st-line treatment of mCRC patients with KRAS wild-type tumours, in combination with chemotherapy. This approval was based on a submission package including data from the initial analysis of the CRYSTAL trial (which investigated the efficacy of cetuximab irrespective of KRAS biomarker status) along with data from the phase II OPUS** trial. Both trials indicated the superior efficacy of cetuximab in combination with standard chemotherapy, compared with chemotherapy alone, in the 1st-line treatment of patients with KRAS wild-type mCRC.2,3

The CRYSTAL trial results come at the same time as data published in the New England Journal of Medicine showing that cetuximab significantly increases overall survival when added to standard chemotherapy in the 1st-line treatment of recurrent and / or metastatic squamous cell carcinoma of the head and neck (SCCHN). The EXTREME*** trial found that the addition of cetuximab led to an increased median overall survival of nearly 3 months (10.1 vs. 7.4 months; p=0.04), equating to a 20% risk reduction of death (HR: 0.80) during the study period. Results also showed a 70% increase in median progression free survival (5.6 vs 3.3 months (p<0.001)) and an 80% relative increase in tumour response rate (36% vs. 20%; p<0.001).4

In June 2008, NICE issued positive guidance on the use of cetuximab (in combination with radiotherapy) for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN).5 A submission to the European authorities to broaden the use of cetuximab to include 1st-line treatment of patients with recurrent and/or metastatic SCCHN was made in June 2008 by Merck Serono and a decision is anticipated in 2009.

In the area of colorectal cancer, cetuximab plus irinotecan has been licensed for irinotecan-refractory mCRC in the EU since June 2004. In the UK however, NICE has so far not approved cetuximab as an option in this indication, on the grounds it is "not compatible with the best use of NHS resources".6 NICE is currently reviewing cetuximab for 1st-line use in patients with mCRC and a decision is expected in April 2009.7

* CRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer
** OPUS: OxaliPlatin and cetUximab in firSt-line treatment of mCRC
*** EXTREME: ErbituX in 1st-line Treatment of REcurrent or MEtastatic head & neck cancer

About ERBITUX®

ERBITUX® (cetuximab) is an IgG1 monoclonal antibody (mAb) targeted to the Epidermal Growth Factor Receptor (EGFR), and was the first mAb to be licensed for use in colorectal cancer in the EU in June 2004. It is manufactured by Merck Serono.

About KRAS

The KRAS gene codes for a protein involved in the EGFR pathway - a complex pathway involved in the development and progression of cancer. In KRAS wild-type tumours, the KRAS protein is only activated in response to certain stimuli, such as EGFR signalling. Erbitux® works by blocking the EGFR signalling pathway, preventing KRAS activation, and subsequent tumour growth. In mutant KRAS tumours, the KRAS protein is permanently activated (regardless of EGFR signalling), therefore the inhibitory effect of Erbitux® is diminished in these cases.

About Bowel Cancer

Bowel cancer is the third most common cancer in the UK, with more than 36,000 people diagnosed each year.8 Five-year survival rates for patients with colorectal cancer have doubled over the last thirty years and are now between 47% and 51%.9

About Head and Neck Cancer

More than 7,800 people are diagnosed with head and neck cancer in the UK every year, the majority of which occur in the mouth, pharynx or tongue.10

About Merck Serono

Merck Serono, the new division for innovative small molecules and biopharmaceuticals of Merck, was established following the acquisition of Serono and the integration of its business with the former Merck Ethicals Division. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, produces and commercializes innovative products to help patients with diseases with unmet needs. Our North American business operates in the United States and Canada under EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®), multiple sclerosis (Rebif®), infertility (Gonal-f®), metabolic and cardiometabolic disorders (Glucophage®, Cardicor®, Saizen®), as well as psoriasis (Raptiva®). With an annual R&D investment of €1bn, we are committed to growing our business in specialist-focused therapeutic areas, such as Neurology and Oncology, as well as new therapeutic areas potentially arising out of our research and development in autoimmune and inflammatory diseases.

For more information, please visit www.merckserono.net or www.merck.de

References:

1. Van Cutsem, et al. ESMO 2008; Abstract No: 710
2. Van Cutsem, et al. ASCO 2008; Abstract No: 2
3. Van Cutsem, et al. ASCO 2008; Abstract No: 4000
4. Vermorken JB, et al. N Engl J Med 2008; 359:1116-27
5. NICE. Cetuximab for the treatment of head and neck cancer. TA145. June 2008.
https://www.nice.org.uk/guidance/index.jsp?action=byID&o=12006 (accessed September 2008)
6. NICE. Bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. TA118. January 2007.
https://www.nice.org.uk/guidance/index.jsp?action=byID&o=11612 (accessed September 2008)
7. NICE. Cetuximab for the first line treatment of metastatic colorectal cancer - in progress.
https://www.nice.org.uk/guidance/index.jsp?action=byID&o=11918 (accessed September 2008)
8. Cancer Research UK. CancerStats Key Facts on Bowel Cancer. How common is large bowel cancer?
http://info.cancerresearchuk.org/cancerstats/types/bowel/ (accessed September 2008)
9. Cancer Research UK. CancerStats Key Facts on Bowel Cancer. Bowel Cancer survival statistics.
http://info.cancerresearchuk.org/cancerstats/types/bowel/survival/?a=5441 (accessed September 2008)
10. Types of head and neck cancer. Cancerbackup website
www.cancerbackup.org.uk/Cancertype/Headneck/General/Typesofheadneckcancer (accessed September 2008)

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