Addressing a presentation by Scott Kopetz, MD, PhD, at the 2013 Chemotherapy Foundation, Howard Hochster, MD, Yale University Cancer Center, New Haven, Connecticut, said he agrees with Dr. Kopetz about the need for expanded RAS testing.
“Now we have two studies suggesting that tumors with all the RAS mutations, including KRAS exons 2, 3, and 4, and NRAS exons 2, 3, and 4, do not benefit from anti–epidermal growth factor receptor (EGFR) antibodies. We need to incorporate these mutations into testing as soon as possible,” Dr. Hochster said in an interview with The ASCO Post.
“The PRIME study suggests that treatment with oxaliplatin-based regimens could be detrimental to patients with those mutations. This makes expanded RAS testing for these mutations all the more compelling,” he stated.
Most physicians who treat colorectal cancer order KRAS testing if they are considering anti-EGFR therapy, he said, which only tests for the common exon 2, codon 12, 13 mutations. This is the FDA-approved test. “They need to request extended RAS testing from their pathologists.” At Yale and some other academic centers, patients with colorectal cancer are profiled for a “snapshot” of more than 120 common mutations. Additionally, a 409-gene profile is available based on next-generation sequencing technology.
“About 40% of colorectal cancer patients harbor KRAS codon 12 and 13, and another 20% will harbor these additional mutations that make them ineligible for anti-EGFR therapy. That is 60% of patients,” Dr. Hochster noted. ■
Disclosure: Dr. Hochster reported no potential conflicts of interest.
Testing for codons 12 and 13 on the KRAS gene and BRAF testing can predict whether patients with colorectal cancer will respond to anti–epidermal growth factor receptor (EGFR) therapies. However, genetic alterations not captured by testing for KRAS codon 12 and 13 mutations may play an important...