When Roche's melanoma drug Zelboraf won the FDA nod in August, it became the first therapy for the disease targeted at patients with a particular genetic abnormality. Scientists now have found another genetic link that stands to affect how Zelboraf is used: Patients with RAS mutations appear to be susceptible to accelerated growth of secondary skin cancers.
The study, published in the latest New England Journal of Medicine, found Zelboraf does not trigger the mutations that cause squamous cell cancers, as previously feared. But the drug does feed their growth in patients with RAS mutations, which probably were caused by sun exposure, researchers said. About one-fourth of patients treated with the drug have developed the secondary cancers, which were removed surgically, MedPage Today reports.
The study showed Zelboraf stimulated mitogen-activated protein kinase signaling, which in turn fueled the proliferation of cells with RAS mutations, MedPage Today points out. Lab mice given an MEK inhibitor saw a 91% reduction in tumor development. So, adding an MEK inhibitor to Zelboraf treatment in patients with those mutations could inhibit the growth of those cancers.
"The combination of BRAF and the MEK inhibitors gives you a better response, and also prevents the emergence of these secondary tumors," lead author Richard Marais, of London's Institute of Cancer Research, told Reuters. As the Wistar Institute's Ashani Weeraratna said in a companion NEJM editorial, "[t]hese data provide a rationale for the use of inhibitors farther down the pathway, such as MEK inhibitors." The new findings suggest that patients beginning treatment with Zelboraf should have their RAS status checked as well, Weeraratna wrote.