Prolonged response to osimertinib in three patients with refractory metastatic pancreatic adenocarcinomas with <i>EGFR</i> exon 19 deletion: a case report and literature review

Pancreatic cancer is a rising cause of cancer death. Therapeutic options are scarce and of limited efficacy. Up to 26% of patients with metastatic pancreatic cancer could benefit from targeted therapies. We report here for the first time the case of three patients with metastatic pancreatic ductal adenocarcinoma (PDAC) without <i>KRAS</i> alteration for whom an activating mutation in exon 19 of the epidermal growth factor receptor (<i>EGFR</i>) gene was found through mainstreaming NGS. The <i>EGFR</i> variant was confirmed on multiple tumor samples and by circulating tumor DNA (ctDNA) analysis in two patients. The three patients were treated with osimertinib with early molecular, biologic, and morpho-metabolic responses. At the last follow-up, one patient had an ongoing response after 17 months, and disease control had been maintained for 8 and 6 months in the other two. Known resistance mechanisms were observed on ctDNA analysis at progression. These observations demonstrate the benefit of osimertinib for treating <i>EGFR</i>-mutated PDAC and highlight the interest in investigating rare molecular alterations, especially in patients without <i>KRAS</i> alterations.