These data were generated from an analysis of the Phase III, randomized, controlled clinical trial that investigated the treatment effect of Vectibix in patients with metastatic colorectal cancer (mCRC). The new biomarker analysis met its primary and secondary endpoints by demonstrating that the effect of Vectibix on PFS was confined exclusively to the approximately 60% of patients whose tumors harbor normal, non-mutated (wild-type) Kras.
No effect of Vectibix therapy was observed in patients who had tumors with mutations in Kras regardless of the endpoint studied. These data have been shared with US and global regulatory agencies and have been submitted for peer-reviewed publication.
Amgen says 20 years of study indicate that Kras plays an important role in cell growth regulation and oncogenesis. In mCRC, the epidermal growth factor receptor (EGFR) transmits signals through a set of intracellular proteins. Upon reaching the nucleus, these signals instruct the cancer cell to reproduce and metastasize, leading to cancer progression.
Anti-EGFR therapies work by blocking the activation of EGFR, thereby inhibiting downstream events that lead to malignant signaling. However, it is hypothesized that in patients with tumors harboring a mutated KRAS gene, the KRAS protein is always turned on, regardless of whether the EGFR has been activated or therapeutically inhibited.
Thus, in patients with mutant KRAS, signaling continues despite anti-EGFR therapy. Activated Kras is detected in approximately 40% of metastatic colorectal cancer, depending on the testing method used. Multiple studies support anti-EGFR therapy being significantly more effective in patients with non-mutated Kras.
In a second analysis, patient samples from four mCRC monotherapy studies of safety and efficacy with Vectibix were used to generate the hypothesis that tumors with mutated Kras are associated with drug resistance. Of the 62 patient samples evaluated in the analysis, 21 had the activated Kras and none responded to therapy. The analysis also found that there was a statistically significant association between Kras mutation status and response to Vectibix.