Erbitux With FOLFIRI Or FOLFOX4 Chemotherapy Helps Advanced Bowel Cancer Patients With WT KRAS Tumours Live Longer

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Main Category: Colorectal Cancer
Also Included In: GastroIntestinal / Gastroenterology;  Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 29 Sep 2009 - 8:00 PDT

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New research presented this month at a major European Oncology meeting has shown previously untreated patients who received the targeted cancer drug Erbitux (cetuximab) along with either FOLFIRI or FOLFOX4 chemotherapy lived up to 4 months longer than patients receiving just the chemotherapy. Patients had cancers showing a particular genetic make-up that responds well to treatment.

The new findings came from combined results (a meta-analysis) of two studies - the large phase III CRYSTAL study and the smaller phase II OPUS study - in which over 1000 patients with advanced (metastatic) colorectal cancer in total participated. Both studies had investigated first-line therapy with and without Erbitux. The CRYSTAL study used a chemotherapy known as FOLFIRI consisting of infused 5FU, leucovorin and irinotecan; the OPUS study used a chemotherapy consisting of infused 5FU, leucovorin and oxaliplatin.

In 845 of the patients, researchers were able to confirm whether patients' tumours had the wild-type KRAS gene, known to respond well to Erbitux, or a mutant KRAS gene which does not. The research was presented at ECCO-ESMO, the joint 15th European Cancer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) congresses, held in Berlin in September 2009 by Professor Eric Van Cutsem of Hospital Gasthuisberg, Leuven, Belgium who was also lead investigator of the CRYSTAL study.

Results showed adding Erbitux to the standard first-line chemotherapies mentioned above, gave a greater than two-fold increase in the chances of tumours responding, and significantly reduced the risk of disease worsening by over one third (34%). The time before this happened was increased by over one month. The risk of dying was reduced by 19 per cent. Median survival for patients from the CRYSTAL study was 23.5 months for patients who added Erbitux to chemotherapy and 20 months for FOLFIRI alone. In the OPUS study median survival for patients who added Erbitux to FOLFOX4 was 22.8 months compared to 18.5 months for FOLFOX4 alone. Median survival, measured here as almost two years, means 50 per cent of patients were likely to live beyond this time. Patients with metastases confined to the liver who respond to Erbitux and who are able to go on to have complete surgical removal of their liver tumours have the chance of being cured of bowel cancer.

Speaking in Berlin Professor Van Cutsem said oncologists were excited by the findings. "These are really important and impressive data," he noted.

A quality of life analysis from patients in the CRYSTAL study was also presented at ECCO-ESMO. It showed that even though Erbitux, an epidermal growth factor receptor (EGFR) inhibitor, produced an acne-like skin rash - a sign the drug is working effectively - this did not adversely affect patients' quality of life or capacity for socialising any more than in patients receiving chemotherapy on its own. Patients receiving Erbitux as well as FOLFIRI chemotherapy reported significantly less nausea and vomiting than patients receiving just FOLFIRI. However there was no significant difference between treatments in best and worse scores for health status overall and in social functioning.

MRC COIN study highlights importance of chemotherapy choice

Preliminary results of another phase III study, the MRC Coin trial, presented at the same meeting tested Erbitux added to different chemotherapies. Two thirds of patients received XELOX which includes the oral drug capecitabine (Xeloda) and oxaliplatin. Patients' tumours also had the WT KRAS genes that typically respond well to Erbitux.

Although responses were increased in patients adding Erbitux to chemotherapy, these regimen (mainly XELOX) did not prove significantly better than the chemotherapy on its own in terms of slowing the process of disease- worsening or enabling patients to live longer. In fact, patients experienced more gastro-intestinal toxicity (diarhhoea) and had to have their chemotherapy dosage substantially reduced. The median survival in this trial, which included more elderly and sick patients than the CRYSTAL and OPUS trials, was 17 months for those adding Erbitux to chemotherapy and 17.9 months for those on chemotherapy alone.

Lead investigator Professor Tim Maughan of Cardiff University told oncologists the implications of the study were that: "We need to be cautious in selecting which partner chemotherapy we use with cetuximab (Erbitux)." Much more analysis has to be carried out on the data from patients in COIN but Professor Maughan said results seem to confirm previous research suggesting that oral capecitabine-based chemotherapy is not as effective or well tolerated when combined with Erbitux as infused 5FU-based chemotherapies like FOLFOX4 and FOLFIRI. More data including the impact of this chemotherapy on patients' quality of life will be presented at a later date.

Erbitux is manufactured and marketed by Merck Serono in Europe and outside the US and Canada. In North America it is marketed by ImClone, a subsidiary of Eli Lilly. Erbitux was first approved for treatment of mCRC by regulators for use in combination with irinotecan-based chemotherapy in 2003.

Written by Olwen Glynn Owen
Glynowen(at)macline.co.uk


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