RAS Mutations Beyond XXXX Exon 2: A Review and Discussion of Clinical Trial Data.

@entity1 @entity470 @entity984 @entity5 @entity14 @entity8497
OPINION STATEMENT: The addition of targeted therapy to a 5-FU chemotherapy backbone is now a standard of care in metastatic @entity14 . @entity470 ( @entity470 ) inhibitors have been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in the first line for @entity1 with @entity5 that do not harbor @entity984 exon 2 mutations. Eligibility criteria for most clinical trials involving @entity470 inhibitors in recent years have used the absence of @entity984 exon 2 mutation as the sole criteria for entry, as this specific mutation has been consistently shown to be predictive of a poor response to @entity470 inhibitors. However, expanded analyses of first-line metastatic trials reveal that other RAS mutations, such as other @entity984 mutations in exons 3 and 4, along with @entity8497 mutations, are predictive of poor responses to @entity470 inhibitors as well. Testing for a full panel of these RAS mutations should be done prior to initiating treatment with an @entity470 inhibitor. Further clinical trials are required to determine the predictive impact of each of these individual mutations. To date, they have been analyzed in the aggregate. The addition of targeted therapy, bevacizumab or an @entity470 inhibitor, to a chemotherapy backbone should be considered for all appropriate @entity1 . The relevant clinical trials that evaluated @entity1 without any RAS mutation and compared an @entity470 inhibitor to chemotherapy alone show a distinct advantage in overall survival and progression-free survival to the groups that received @entity470 inhibition. The largest trial that compared bevacizumab with an @entity470 inhibitor in the first line, CALGB/SWOG 80405, did not show a statistically significant difference between the two groups, making the use of bevacizumab, cetuximab, or panitumumab reasonable in the first line.
