Case report outcome of cetuximab treatment in a metastatic colorectal cancer patient with novel KRAS P34R

Cetuximab [the epidermal growth factor receptor (EGFR)-targeting mAb] improves clinical outcomes when added to standard chemotherapy used in the treatment of metastatic colorectal cancer. Patients with hotspot mutations in Kirsten rat sarcoma viral oncogene ( KRAS ) mutation in exon 2 were not recommended to be treated with cetuximab. However, there is still a lack of clinical data for those unreported non-hotspot KRAS mutations in exon 2 and their response to cetuximab. In this study, we reported a 35-year-old woman who was diagnosed with stage IVA CRC with liver metastases. An exceptionally uncommon KRASP34R mutation in KRAS exon 2 was detected in tumor specimens by next-generation sequencing. This patient obtained limited benefit from first-line chemotherapy and did not respond to cetuximab in the second-line course. In the third-line course, the patient also did not respond to the combination treatment of furaquitinib and cindilimab. The patient died 8 months after treatment initiation. In this study, we found amplification of the rare oncogenic KRASP34R was not only associated with an aggressive phenotype, but also supported cancer resistance to cetuximab, chemotherapy, and immunotherapy.