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 20 February 2018

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Treatment to improve overall survival for KRAS wild-type advanced colorectal cancer

This week's issue of the Journal of the American Medical Association examines the effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer.

News image

Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown.

Dr Alan Venook and colleagues determined if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type colorectal cancer.

Patients enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wild-type chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab or bevacizumab.

The median overall survival was 30 months in the cetuximab-chemotherapy group
Journal of the American Medical Association

The researchers compared cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient.

The team's primary end point was overall survival.

Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response.

Among 1137 patients, the researchers found that 94% of patients met eligibility criteria.

As of 2015, median follow-up for 263 surviving patients was 47 months, and 82% of patients experienced disease progression.

The team found that the median overall survival was 30 months in the cetuximab-chemotherapy group, and 29 months in the bevacizumab-chemotherapy group with a stratified hazard ratio of 0.88.

The research team noted that the median progression-free survival was 11 months in the cetuximab-chemotherapy group and in the bevacizumab-chemotherapy group with a stratified hazard ratio of 0.95.

The research team observed that response rates were not significantly different, 60% vs 55% for cetuximab and bevacizumab, respectively.

Dr Venook's team comments, "Among patients with KRAS wild-type untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment."

JAMA 2017;317(23):2392-2401
23 June 2017

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