Vigié Timothée, Perrier Alexandre, Chanez Brice, De Martino Julien, Favre Loëtitia, Coulet Florence, Bachet Jean-Baptiste, Guillerm Erell, Mas Léo
Hepato-Gastroenterology and Digestive Oncology Department, Sorbonne University, Pitié Salpêtrière Hospital, AP-HP, Paris, France.
Genetics Medical Department, Sorbonne University, Pitié Salpêtrière Hospital, AP-HP, Paris, France.
Ther Adv Med Oncol. 2025 Mar 28;17:17588359241312078. doi: 10.1177/17588359241312078. eCollection 2025.
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 alteration for whom an activating mutation in exon 19 of the epidermal growth factor receptor () gene was found through mainstreaming NGS. The 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 -mutated PDAC and highlight the interest in investigating rare molecular alterations, especially in patients without alterations.
胰腺癌是癌症死亡人数不断上升的一个原因。治疗选择稀缺且疗效有限。高达26%的转移性胰腺癌患者可从靶向治疗中获益。我们在此首次报告3例转移性胰腺导管腺癌（PDAC）患者的病例，这些患者没有[具体基因名称]改变，但通过二代测序（NGS）主流检测发现其表皮生长因子受体（EGFR）基因第19外显子存在激活突变。该变异在多个肿瘤样本中得到证实，并且在两名患者中通过循环肿瘤DNA（ctDNA）分析得到确认。这3例患者接受了奥希替尼治疗，出现了早期分子、生物学和形态代谢反应。在最后一次随访时，1例患者在17个月后仍有持续反应，另外两名患者的疾病控制分别维持了8个月和6个月。在疾病进展时的ctDNA分析中观察到了已知的耐药机制。这些观察结果证明了奥希替尼治疗EGFR突变型PDAC的益处，并突出了研究罕见分子改变的意义，特别是在没有[具体基因名称]改变的患者中。
