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Extended RAS testing looks for mutations across KRAS and NRAS, not just the one spot that was tested first. It decides who can have an EGFR antibody: the drugs work only when every one of those spots is normal, and testing the wider set moved about one patient in six out of the group offered them.
Why the test was widened. Cetuximab and panitumumab were first restricted to tumours without a KRAS exon 2 (codon 12 and 13) mutation. The PRIME trial's prospective-retrospective analysis tested a further set in patients whose KRAS exon 2 was normal: KRAS exons 3 and 4, NRAS exons 2, 3 and 4, and BRAF exon 15. Of 639 patients with results, 108 (17 percent) carried one of the other RAS mutations, and in those patients adding panitumumab to FOLFOX4 did harm rather than good, exactly as in KRAS exon 2-mutant disease. Among the 512 with no RAS mutation anywhere, panitumumab with FOLFOX4 gave a median progression-free survival of 10.1 against 7.9 months and median overall survival of 26.0 against 20.2 months (Douillard 2013). BRAF mutation was prognostic rather than predictive in that analysis.
What is tested now. NICE NG151 (1.4.1) says to test for RAS and BRAF V600E mutations in everyone with metastatic colorectal cancer who is suitable for systemic anticancer treatment. A tumour with no mutation across the extended RAS set is described as RAS wild-type, which is the eligibility criterion for an EGFR antibody; sidedness then decides whether the antibody is likely to help, because the benefit is confined to left-sided tumours.
A gap worth naming. RAS wild-type status is a predictive readout in its own right and the corpus has no biomarker record for it; this glossary term is the explainer until one exists. Resistance mutations in RAS, BRAF and EGFR that appear in the blood during treatment are the basis of the rechallenge strategy, which has its own term.
In plain words · KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.
Showing the target this term concerns: KRAS.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Shares Sidedness (left vs right colon), BRAF, EGFR, KRAS and the tags gi, colorectal.
Shares Germline vs somatic mutations, Comprehensive genomic profiling, Colon cancer (adenocarcinoma of the colon), Rectal cancer and the tags gi, colorectal.
Shares Sidedness (left vs right colon), BRAF V600E-mutant colorectal cancer, BRAF, Colon cancer (adenocarcinoma of the colon) and the tags gi, colorectal.
Shares Germline vs somatic mutations, Colon cancer (adenocarcinoma of the colon), Rectal cancer, Colorectal cancer and the tags gi, colorectal.
Shares Sidedness (left vs right colon), Colon cancer (adenocarcinoma of the colon), Rectal cancer, Colorectal cancer and the tags gi, colorectal.
Shares Circulating tumour DNA (ctDNA), Colon cancer (adenocarcinoma of the colon), Rectal cancer, Colorectal cancer and the tags gi, colorectal.
Shares BRAF V600E-mutant colorectal cancer, BRAF, KRAS, Colon cancer (adenocarcinoma of the colon) and the tags gi, colorectal.
Shares Colon cancer (adenocarcinoma of the colon), Rectal cancer, Colorectal cancer and the tags gi, colorectal.