Introduction: The prognosis of pancreatic cancer has improved only modestly in recent years. This is partly due to the lack of development in precision oncology including immune oncology in this entity. Rearrangements of the proto-oncogene tyrosine protein kinase ROS1 gene represent driver alterations found especially in lung cancer. Tyrosine kinase inhibitors (TKI) with activity against ROS1 including lorlatinib substantially improved the outcome of this patient population. Anecdotal evidence reports treatment of pancreatic cancer harboring ROS1 fusions with ROS1 TKI, but data concerning treatment of patients with ROS1 point mutations are lacking. Case Presentation: This case describes a pancreatic cancer patient harboring a ROS1 point mutation that occurred without an underlying ROS1 rearrangement and thus not in the resistance situation. The heavily pretreated patient showed a strong decrease of the tumor biomarkers (CA19-9 and CEA) and radiologically a durable stable disease to the targeted treatment with lorlatinib, thereby achieving a progression-free survival of 12 months. Conclusion: Our data are the first to show a clinical benefit from targeted treatment with ROS1 TKI in a cancer patient with a thus far undescribed ROS1 point mutation without a concomitant ROS1 rearrangement. Furthermore, they indicate that ROS1 could be an oncogenic driver in pancreatic cancer. This subgroup could be eligible for targeted treatments, which may contribute to the urgently needed improvement in patient outcome.
Oncol Res Treat

中文翻译：

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劳拉替尼在具有 ROS1 p.L1950F 突变的胰腺癌患者中诱导持久的疾病稳定：病例报告

简介：近年来，胰腺癌的预后仅略有改善。这部分是由于该实体的精准肿瘤学（包括免疫肿瘤学）缺乏发展。原癌基因酪氨酸蛋白激酶ROS1基因的重排代表了特别是在肺癌中发现的驱动改变。包括劳拉替尼在内的具有 ROS1 活性的酪氨酸激酶抑制剂 (TKI) 显着改善了该患者群体的结果。轶事证据报告了用 ROS1 TKI治疗携带ROS1融合的胰腺癌，但缺乏有关治疗ROS1点突变患者的数据。案例介绍：本案例描述了一名患有 ROS1点突变的胰腺癌患者，该突变没有潜在的ROS1重排，因此不处于耐药情况。严重预处理的患者显示肿瘤生物标志物（CA19-9 和 CEA）显着降低，放射学上对劳拉替尼的靶向治疗是一种持久稳定的疾病，从而实现了 12 个月的无进展生存期。结论：我们的数据首次显示了 ROS1 TKI 靶向治疗对具有迄今为止未描述的ROS1点突变且没有伴随ROS1重排的癌症患者的临床益处。此外，他们表明ROS1可能是胰腺癌的致癌驱动因素。该亚组可能有资格接受靶向治疗，这可能有助于迫切需要改善患者的预后。
肿瘤资源治疗