Comparative Effectiveness Study Examines Treatment Options for Type of Colorectal Cancer

A recent study compared the effects of first-line chemotherapy with two different drugs in patients with advanced or metastatic colorectal cancer, published in JAMA (2017;317[23]:2392-2401).


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Previous research has shown that combining biologic monoclonal antibodies with chemotherapy cytotoxic drugs improves clinical outcomes for patients with advanced or metastatic colorectal cancer. However, the optimal antibody for such combination regimens in previously untreated patients has yet to be determined.

Alan P Venook, MD, University of California, San Francisco, and colleagues conducted a comparative effectiveness study involving two different first-line regimens in advanced or metastatic KRAS wild-type colorectal cancer. Researchers tested the effects of adding cetixumab or bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen in 1137 patients (median age, 59 years) throughout the National Clinical Trials Network in the United States and Canada from 2005 to 2012.

Primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS) and overall response rate (ORR).

Median follow-up for the 263 surviving patients (as of December 2015) was 47.4 months (range, 0-110.7 months). Eighty-two percent of patients experienced disease progression.

Researchers observed comparable effects between the cetixumab and bevacizumab regimens. Median OS was 30.0 months in the cetuximab plus chemotherapy group and 29.0 months in the bevacizumab plus chemotherapy group (HR, 0.88; 95% CI, 0.77-1.01; P = .08). Median PFS was nearly identical in the two groups (10.5 months vs 10.6 months, respectively; HR, 0.95; 95% CI, 0.84-1.08; P = .45) and ORR was not significantly different (59.6% vs 55.2%; 95% CI, 1.0%-9.0%; P = .13).

Authors of the study concluded that neither cetixumab or bevacizumab demonstrated a clinically significant OS advantage for initial treatment of advanced or metastatic KRAS wild-type colorectal cancer. Further research is needed to determine an optimal antibody for first-line combination regimens in this disease.—Zachary Bessette