When KRAS mutations were found to thwart a response to EGFR-targeted therapies, such as Erbitux (cetuximab) and Vectibix (panitumumab), it was a practice-changing discovery in colorectal cancer. (You can read more about colorectal cancer treatment and the use of personalized medicine in CURE here.) Research presented at an oncology meeting held earlier this month on additional mutations may result in yet another change in the way we treat colorectal cancer.
About 40 to 50 percent of colorectal cancers harbor mutations in a particular part of the KRAS gene called exon 2. (An exon is a genetic piece of information that codes for a protein. If the protein isn’t coded correctly, it could turn on cancer growth.)
Researchers have learned that patients with colorectal cancer that contain a KRAS exon 2 mutation are not helped by EGFR-targeted therapies. The plus side is physicians can now test for this biomarker to identify these patients, shielding them from the toxicities and cost of a treatment that wouldn’t work, and instead focus on other therapies, such as anti-angiogenic drugs.
Recent studies lend more evidence that it is not a single mutation that affects a tumor’s response to Vectibix, but an even wider range of mutations.
A phase 3 study presented at the American Society of Clinical Oncology’s Gastrointestinal Symposium analyzed the response of metastatic colorectal cancers to second-line chemotherapy with or without the EGFR-targeting drug Vectibix. Tumors were analyzed for KRAS mutations in exons 1-4 and NRAS exons 1-4, collectively known as RAS mutations.
Although the majority of mutations were in KRAS exon 2, an additional 18 percent of tumors were found to harbor one of these other mutations. (You can view the abstract here.) Patients with these additional mutations, much like those patients with a KRAS exon 2 mutation, did not benefit from the addition of Vectibix.
In essence, a patient’s tumor could test negative for the mutation in KRAS exon 2 and be prescribed Vectibix. However, if the tumor contains one of these other mutations, the treatment would still fail to work. While this study confirmed what researchers have seen in other studies in newly diagnosed advanced colorectal cancer, this was the first large study that showed a similar effect in second-line therapy.
“Based on all the data that we generated, it’s clear that today we need RAS testing instead of KRAS exon 2 testing before embarking on an anti-EGFR treatment in patients with metastatic colorectal cancer,” said lead researcher Marc Peeters, of Antwerp University Hospital in Belgium, as he concluded his presentation to other gastrointestinal oncologists at the meeting.
Experts expect that expanded RAS testing will soon become the standard of care in treating patients with metastatic colorectal cancer.