Erbitux Edges Avastin for First-Line Colorectal Cancer Therapy

Editor’s note: This article discusses the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to compare two drugs—bevacizumab and cetuximab—when they were added to the standard chemotherapy combo FOLFIRI. All patients who participated in the trial had metastatic colorectal cancer. The researchers found that patients treated with FOLFIRI plus cetuximab had longer overall survival times that patients treated with FOLFIRI plus bevacizumab. The results differ from those from another recent study, which found no significant difference between the two treatments.

“Adding cetuximab (Erbitux) to the standard first-line FOLFIRI chemotherapy regimen resulted in longer overall survival compared with FOLFIRI plus bevacizumab (Avastin) in patients with metastatic colorectal cancer, according to results of the phase III FIRE-3 trial published this month in the Lancet.

“This result was seen in patients with a wild-type exon 2 KRAS gene. The longer overall survival was observed despite there being no significant difference in objective response between the two study groups.

“The study analyzed data from 592 patients with KRAS exon 2 wild-type colorectal cancer treated with FOLFORI and either cetuximab (an epidermal growth factor receptor inhibitor) or bevacizumab (an angiogenesis inhibitor). Patients were recruited at 116 Austrian and German cancer centers.”


Higher Bar Set for Trials in Advanced Colorectal Cancer

Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to compare four different treatments for metastatic colorectal cancer (mCRC). All patients took a combination of chemotherapy drugs; either FOLFIRI [which combines folinic acid, fluorouracil and irinotecan] or FOLFOX [folinic acid, 5-fluorouracil and oxaliplatin]. Patients also took a targeted drug alongside the chemo; either bevacizumab (aka Avastin) or cetuximab (Erbitux). All four treatment combinations resulted in similar survival times—a median of 29 months. Compared to other clinical trials, this is a relatively long survival time. Based on these results, oncologists will now have more options for treating their patients according to patients’ preferences and side effects.

“Patients with KRAS wild-type metastatic colorectal cancer (mCRC) receiving first-line treatment with a chemotherapy backbone plus bevacizumab or cetuximab survived for a median of 29 months, the longest median survival time reported in a major trial of these severely ill patients.

“Importantly, survival times were the same, whether patients received the anti–vascular endothelial growth factor bevacizumab (Avastin, Genentech) or the anti–epidermal growth factor receptor (EGFR) cetuximab (Erbitux, Bristol-Myers Squibb), or whether they received FOLFOX or FOLFIRI, results from the long-awaited Phase III CALGB/SWOG 80405 trial showed.

“ ‘What this tells us is that either FOLFIRI [folinic acid, fluorouracil and irinotecan] or FOLFOX [folinic acid, 5-fluorouracil and oxaliplatin] with either bevacizumab or cetuximab are perfectly reasonable options,’ said Alan P. Venook, MD, the Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California, San Francisco.”


No Difference in Response Rate but Overall Survival Benefit With First-Line FOLFIRI/Cetuximab vs FOLFIRI/Bevacizumab in Metastatic Colorectal Cancer

Editor’s note: Researchers organized a clinical trial with volunteer patients to compare two treatments for people with metastatic colorectal cancer. All patients in the trial took a chemotherapy treatment called FOLFIRI. (FOLFIRI combines the drugs fluorouracil, leucovorin, and irinotecan.) Some of the patients were also given the drug cetuximab, and the rest took the drug bevacizumab along with FOLFIRI. The patients who took FOLFIRI plus cetuximab survived significantly longer than the patients who took FOLFIRI plus bevacizumab.

“In a European phase III FIRE-3 trial reported in The Lancet Oncology, Heinemann et al found no difference in response rate, the primary endpoint, between FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus the anti-EGFR antibody cetuximab (Erbitux) vs FOLFIRI plus the anti-VEGF-A antibody bevacizumab (Avastin) in first-line treatment of patients with metastatic colorectal cancer. The cetuximab-containing regimen was associated with a significant overall survival advantage…

“In this open-label trial, 592 patients with KRAS exon 2 codon 12/13 wild-type metastatic colorectal cancer aged 18 to 75 years from centers in Germany and Austria were randomly assigned between January 2007 and September 2012 to receive FOLFIRI plus either cetuximab (n = 297) or bevacizumab (n = 295). The primary endpoint was objective response in the intention-to-treat population. The study has completed recruitment, but patient follow-up is ongoing.”


Cetuximab or Bevacizumab with Combi Chemo Equivalent in KRAS Wild-Type MCRC

“For patients with KRAS wild-type untreated colorectal cancer, adding cetuximab or bevacizumab to combination chemotherapy offers equivalent survival, researchers said at the ESMO 16th World Congress on Gastrointestinal Cancer in Barcelona.” ‘The CALGB/SWOG 80405 trial was designed and formulated in 2005, and the rationale was simple: we had new drugs —bevacizumab and cetuximab— and the study was designed to determine if one was better than the other in first-line for patients with colon cancer,’ said lead study author Alan P. Venook, distinguished Professor of Medical Oncology and Translational Research at the University of California, San Francisco, USA.

“The CALGB/SWOG 80405 trial studied patients whose tumours were KRAS wild-type at codons 12 and 13. Patients received mFOLFOX6 or FOLFIRI at the discretion of their doctor and were randomised to cetuximab (578 patients) or bevacizumab (559 patients).

” ‘There was no meaningful difference in outcome between treatment arms,’ said Venook. ‘In both arms patients lived close to 30 months. About 10% of patients lived more than 5 years. Overall patients did much better than anticipated and it was indifferent to the type of treatment.’ ”

Editor’s note: This story discusses the results of a clinical trial that tested a treatment for colorectal cancer in volunteer patients without mutations in the KRAS gene in their tumors (as detected by molecular testing). The goal of the trial was to compare two chemotherapy drugs—bevacizumab and cetuximab—to see whether one is better than the other as a first-line colorectal cancer for so-called “KRAS wild-type” colorectal cancer. The results showed that there was no significant difference between the two.