Josep Tabernero, MD, PhD, Head of Medical Oncology and the Institute of Oncology at Vall d’Hebron University Hospital in Barcelona, Spain, discussed the results of CALGB/SWOG 80405 at the ASCO Plenary Session.

“CALGB/SWOG 80405 did not meet the primary endpoint of superiority [for cetuximab] in a population of patients with KRAS exon 2 wild-type tumors. Nevertheless, I am reluctant to describe this as a negative study, because it is very informative and, with additional analyses, the interpretation may change,” Dr. Tabernero said.

“FOLFOX/cetuximab and FOLFOX/bevacizumab seem comparable in this setting, although a slight trend favoring cetuximab arm may be seen in the second part of the [survival] curve. FOLFIRI/cetuximab and FOLFIRI/bevacizumab seem comparable, but the FOLFIRI results may be less robust, as they account for only one-fourth of the population,” he observed.

More Data Essential

He said the future presentation of overall response rates, depth of response, degree of tumor shrinkage, and other factors “will be important in order to obtain essential knowledge regarding the initial effects of the treatment on tumor burden.”

Similarly, he urged the FIRE-3 investigators to “present as soon as possible” that study’s other efficacy data. “It is very difficult indeed to understand differences in overall survival without any difference in response rate or progression-free survival.” He would like to see the independent review of response, evidence of tumor shrinkage, and depth of response “to help us understand the different effect in overall survival,” he said.

In CALGB/SWOG 80405, expanded RAS testing—looking for KRAS mutations in exons 3 and 4, and NRAS mutations—will be highly informative and could change the results, he predicted, figuring that expanded RAS analysis could narrow the population from 1,137 to 900 or 975 RAS wild-type patients, and alter the overall survival hazard ratio from 0.92 to 0.87–0.85.

“For the time being,” he said, “We cannot conclude that there is specific evidence for a regimen sequence for the KRAS wild-type exon 2 population, though there are emerging data that can be utilized on an individual basis.”

“The results of CALGB/SWOG 80405 mark an important milestone in the roadmap of metastatic colorectal cancer treatment,” he said. Future analyses, he added, “will shed light on the important questions that remain unanswered.” ■

Disclosure: Dr. Tabernero is a consultant and/or advisor for Amgen, ImClone, Lilly, Merck KGaA, Millennium, Novartis, Roche, Sanofi, Celgene, Chugai, and Taiho.