Final overall survival improvement of 3.5 months compared with standard chemotherapy − updated analysis from pivotal CRYSTAL trial published in the Journal of Clinical Oncology shows KRAS is the only validated biomarker which is predictive for the efficacy of Erbitux.

An updated analysis of the Phase III CRYSTALa* study has been published in the latest edition of the Journal of Clinical Oncology. The analysis included the evaluation of overall survival (OS) according to KRAS mutation status in patients with metastatic colorectal cancer (mCRC), and found that the addition of Erbitux (cetuximab) to standard chemotherapy (FOLFIRI) in patients with KRAS wild-type disease resulted in a significant improvement in OS of 3.5 months, compared with FOLFIRI alone.¹ CRYSTAL is the only trial to date to² demonstrate a significant overall survival benefit of a targeted therapy in combination with current standard chemotherapy (FOLFIRI) in 1st line treatment of mCRC.

Professor David Cunningham, lead UK Investigator in CRYSTAL, from the Royal Marsden NHS Foundation Trust, commented, "These results demonstrate a clear survival benefit from the addition of cetuximab to FOLFIRI in patients receiving first-line chemotherapy for metastatic colorectal cancer where the tumour is known to have an unmutated KRAS gene. These findings will be relevant for up to 60% of patients with metastatic colorectal cancer and funding arrangements are already in place through the Cancer Drugs Fund for most patients to receive this treatment if it is deemed appropriate by the clinical team."

CRYSTAL is a multi-centre, Phase III, randomised, controlled trial involving 1,198 patients and investigating the efficacy and safety of Erbitux in combination with FOLFIRI vs. FOLFIRI alone in the 1st line treatment of patients with mCRC.

"CRYSTAL was the first Phase III trial to demonstrate the significance of the KRAS biomarker in 1st line mCRC. The findings have since led to a critical shift towards more personalised management of this disease and, most importantly, to improved outcomes for patients," added Dr. Wolfgang Wein, Executive Vice President, Oncology, Merck Serono. "We are proud of the contribution the study has made to science and to patient care."

The top-line CRYSTAL results1 in patients with KRAS wild-type tumours (n=666) receiving Erbitux plus FOLFIRI are:

Median OS was 23.5 months compared to 20.0 months in those receiving chemotherapy alone (Hazard Ratio [HR] 0.796; p=0.0093)The risk of disease progression was reduced by 30.4% (HR 0.696; p=0.0012). The likelihood of achieving a tumour response doubled overall (Odds Ratio [OR] 2.0693; ORR 57.3% vs. 39.7%; p<0.001)

In 2008, the CRYSTAL study was recognised by the American Society of Clinical Oncology (ASCO) as one of the "major clinical cancer advances" for the year.

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.³ Approximately 25% of patients present with metastatic disease,⁴ and 5-year survival rates for patients with mCRC can be as low as 5%.⁵


Source: MERCK

References

1. Van Cutsem E, et al. J Clin Oncol 2011 Apr. 10.1200/JCO.2010.33.5091

2. Winer E, et al. J Clin Oncol. 2009 Feb 10;27(5):812-26.

http://jco.ascopubs.org/content/27/5/812.full.

3. Parkin DM, et al. CA Cancer J Clin 2005;55:72–108.

4. Cunningham D, et al. Eur J Cancer 1993;29A(15):2077–2079.

5. Macdonald JS. CA Cancer J Clin 1999;49(4):202–219.

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