Department of Medical Oncology, Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland.
Department of Medical Oncology and Hematology, Cantonal Hospital Schaffhausen, Schaffhausen, Switzerland.
Cancer Treat Rev. 2021 May;96:102180. doi: 10.1016/j.ctrv.2021.102180. Epub 2021 Mar 17.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with a dismal prognosis. The lack of symptoms in the early phase of the disease makes early diagnosis challenging, and about 80-85% of the patients are diagnosed only after the disease is locally advanced or metastatic. The current front-line treatment landscape in local stages comprises surgical resection and adjuvant chemotherapy. In Switzerland, although both FOLFIRINOX and gemcitabine plus nab-paclitaxel regimens are feasible and comparable in the first-line setting, FOLFIRINOX is preferred in the treatment of fit (Eastern Cooperative Oncology Group [ECOG] performance status [PS]: 0-1), young (<65 years old) patients with few comorbidities and normal liver function, while gemcitabine plus nab-paclitaxel is used to treat less fit (ECOG PS: 1-2) and more vulnerable patients. In the second-line setting of advanced PDAC, there is currently only one approved regimen, based on the phase III NAPOLI-1 trial. Furthermore, the use of liposomal-irinotecan in the second line is supported by real-world data. Beyond the standard of care, various alternative treatment modalities are being explored in clinical studies. Immunotherapy has demonstrated only limited benefits until now, and only in cases of high microsatellite instability (MSI-H). However, data on the benefit of poly (ADP-ribose) polymerase (PARP) inhibition as maintenance therapy in patients with germline BRCA-mutated tumors might signal of an advance in targeted therapy. Currently, there is a lack of molecular and genetic biomarkers for optimal stratification of patients and in guiding treatment decisions. Thus, identification of predictive and prognostic biomarkers and evaluating novel treatment strategies are equally relevant for improving the prognosis of metastatic pancreatic cancer patients.
胰腺导管腺癌 (PDAC) 是一种侵袭性癌症，预后极差。疾病早期缺乏症状，使得早期诊断具有挑战性，约 80-85%的患者仅在疾病局部晚期或转移时才被诊断。目前，局部阶段的一线治疗方案包括手术切除和辅助化疗。在瑞士，虽然 FOLFIRINOX 和吉西他滨加 nab-紫杉醇方案在一线治疗中都可行且相当，但 FOLFIRINOX 更适用于适合（东部合作肿瘤学组 [ECOG] 表现状态 [PS]：0-1）、年轻（<65 岁）、合并症少且肝功能正常的患者，而吉西他滨加 nab-紫杉醇则用于治疗状态较差（ECOG PS：1-2）和更脆弱的患者。在晚期 PDAC 的二线治疗中，目前只有一种基于 III 期 NAPOLI-1 试验的批准方案。此外，基于真实世界数据，二线使用脂质体伊立替康也得到了支持。在标准治疗之外，各种替代治疗方法正在临床研究中进行探索。免疫疗法到目前为止仅显示出有限的益处，并且仅在高度微卫星不稳定（MSI-H）的情况下。然而，关于聚（ADP-核糖）聚合酶（PARP）抑制剂作为胚系 BRCA 突变肿瘤患者维持治疗的益处的数据可能预示着靶向治疗的进步。目前，缺乏用于最佳分层患者和指导治疗决策的分子和遗传生物标志物。因此，鉴定预测和预后生物标志物以及评估新的治疗策略对于改善转移性胰腺癌症患者的预后同样重要。
