JAMAThe cancer-treatment agent cetuximab is believed to be an ineffective treatment for KRAS (a gene)-mutated metastatic colorectal tumors. A new study now shows that colorectal cancer patients who did not respond to chemotherapy and a certain variation of this gene, when treated with cetuximab displayed longer overall and progression-free survival than those with other KRAS-mutations.

“Recent retrospective correlative analyses of metastatic colorectal cancer trials indicate that patients with KRAS-mutated tumors do not benefit from the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab,” according to the authors.

The authors further add that there are signs which show that not all KRAS mutations are identical in their biological traits. Moreover, anecdotal reports have shown that a minority of individuals inflicted with KRAS-mutated tumors are capable of responding to anti-EGFR therapy. A study had been conducted by Wendy De Roock, M.D., of the University of Leuven, Leuven, Belgium, and colleagues to investigate whether a certain KRAS mutation (p.G13D) could be related to a more positive outcome after cetuximab treatment than seen in the case of other KRAS mutations.

The study comprised of a compiled data from 579 patients with chemotherapy-refractory (not responsive to treatment) colorectal cancer treated with cetuximab from 2001 to 2008. These were individuals who had been included in other clinical trials or were recipients of off-study treatment. The efficacy outcome measures were, first the overall survival, while the secondary ones were progression-free survival and response rate.

“In a large, retrospective pooled exploratory analysis of patients with chemotherapy-refractory colorectal cancer, we show for the first time that there is a positive association between KRAS p.G13D mutations and cetuximab treatment in regard to better overall and progression-free survival,” stated the authors.

However, they have added, “Prospective randomized trials are needed before conclusions about potential beneficial effects of cetuximab in p.G13D-mutated chemotherapy-refractory metastatic colorectal cancer should be inferred.”

Investigators discovered that overall and progression-free survival was significantly longer in patients with p.G13D-mutated tumors when they received any cetuximab-based treatment (cetuximab monotherapy or cetuximab plus chemotherapy) (n = 571). These patients had scored an overall survival (n=32) median, amounting 7.6 months and a progression-free survival of (n=32) median coming to 4.0 months. On the other hand those with other KRAS-mutated tumors showed an overall survival: median, 5.7 months and progression-free survival: median, 1.9 months.

Authors have further elucidated that this outcome may not be because of a real reduction in tumor burden but due to a delay in progression. This study appears in the October 27 issue of JAMA.