Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer
Whole-genome and RNA sequencing of pancreatic cancers in younger patients found that most of the tumours without a KRAS mutation instead carried a fusion of the NRG1 gene, and two patients given a HER-family blocker responded. It established NRG1 fusions as the driver to look for in KRAS wild-type pancreatic cancer.
Overview
Report from the German NCT/DKTK MASTER precision oncology programme on whole-genome and transcriptome sequencing of pancreatic ductal adenocarcinomas from young patients (50 or under). Among the tumours without a KRAS mutation, most harboured an NRG1 gene fusion, whereas no KRAS-mutant tumour did.
Two patients with NRG1 fusion-positive tumours treated with the ERBB inhibitor afatinib had clinical and radiological responses, providing the first evidence that these fusions are actionable in pancreatic cancer and that RNA-level analysis is needed to find them.
- NRG1 fusions were found in most KRAS wild-type pancreatic cancers in a young-onset cohort and in none of the KRAS-mutant tumours.
- Two patients with NRG1 fusion-positive tumours responded to afatinib.
KRAS wild-type status should trigger fusion testing, ideally by RNA sequencing, because NRG1 fusions can be targeted by HER-family inhibitors and now by zenocutuzumab.
- A small, young-onset cohort; the frequency of NRG1 fusions in unselected KRAS wild-type disease is lower.
- Afatinib responses were anecdotal and often short.
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