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Combination vs. Sequential Escalation Therapy for Metastatic Colorectal Cancer

By: Lauren Harrison, MS
Posted: Tuesday, January 22, 2019

Sequential escalation therapy did not demonstrate noninferiority when compared with initial combination chemotherapy for patients with metastatic colorectal cancer, according to the phase III XELAVIRI trial published in the Journal of Clinical Oncology. Dominik Paul Modest, MD, of the Klinikum Grosshadern at the University of Munich, and his colleagues also suggest that RAS status may be an important determination in deciding between these treatment strategies.

From December 2019 to August 2016, 421 patients from 82 sites in Germany were randomly assigned to receive fluoropyrimidine and bevacizumab with the addition of irinotecan at first disease progression or an upfront combination of all three agents at once. Time to failure of the strategy was compared for each of the 2 arms, and noninferiority could not be shown at a margin of 0.8. The time to failure of the strategy for the sequential group was 9.6 months versus 9.9 months in the combination group (hazard ratio = 0.86). Overall survival was similar in both groups.

The authors noted that the upfront combination provided a better time to failure of the strategy for patients with RAS/BRAF wild-type disease than did sequential therapy, 12.6 versus 9.1 months, respectively. Those with RAS-mutant disease experienced no benefit from the upfront combination therapy. In terms of toxicity, there was a small difference in the incidence of grade 3 or higher events between the two groups (80.7% with sequential therapy and 77.1% with combination therapy).

Disclosure: The study authors’ disclosure information may be found at

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