Department of Internal Medicine I, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
Curr Treat Options Oncol. 2021 Oct 19;22(11):106. doi: 10.1007/s11864-021-00895-4.
Pancreatic cancer is mainly diagnosed at an advanced, often metastatic stage and still has a poor prognosis. Over the last decades, chemotherapy of metastatic pancreatic cancer (mPDAC) has proven to be superior to a mere supportive treatment with respect to both survival and quality of life. Recently, even sequential treatment of mPDAC could be established. Options for first-line treatment are combination chemotherapy regimens such as FOLFIRINOX and gemcitabine plus nab-paclitaxel when the performance status of the patient is good. For patients with poorer performance status, gemcitabine single-agent treatment is a valid option. Recently, the PARP inhibitor olaparib has been demonstrated to improve progression-free survival when used as a maintenance treatment in the subgroup of patients with mPDAC and a BRCA1/-2 germ line mutation having received at least 16 weeks of platinum-based chemotherapy. This group of patients also benefits from platinum-based chemotherapy combinations. Therefore, the BRCA1/-2 stats should be examined early in patients with mPDAC even when the occurrence of these mutations is only about 5% in the general Caucasian population. After the failure of first-line treatment, patients should be offered a second-line treatment if their ECOG permits further treatment. Here, the combination of 5-FU/FA plus nanoliposomal irinotecan has shown to be superior to 5-FU/FA alone with respect to overall survival. Immune checkpoint inhibitors like PD1/PD-L1 mAbs are particularly efficacious in tumors with high microsatellite instability (MSI-h). Limited data in mPDACs shows that only a part of the already small subgroup of MSI-H mPDACs (frequency about 1%) appears to benefit substantially from a checkpoint inhibitor treatment. The identification of further subgroups, e.g., tumors with DNA damage repair deficiency, gene fusions, as well as novel approaches such as tumor-organoid-informed treatment decisions, may further improve therapeutic efficacy.
胰腺癌主要在晚期诊断，通常已经转移，预后仍然较差。在过去的几十年中，转移性胰腺癌（mPDAC）的化疗在生存和生活质量方面都优于单纯的支持治疗。最近，甚至可以建立 mPDAC 的序贯治疗。一线治疗的选择包括 FOLFIRINOX 和吉西他滨加 nab-紫杉醇联合化疗方案，如果患者的体能状况良好。对于体能状况较差的患者，吉西他滨单药治疗是一种有效的选择。最近，PARP 抑制剂奥拉帕利在接受至少 16 周铂类化疗的 mPDAC 患者亚组中作为维持治疗使用时，已被证明可改善无进展生存期。这组患者也从铂类化疗联合中获益。因此，即使在普通白种人群中这些突变的发生率仅约为 5%，也应在 mPDAC 患者中尽早检查 BRCA1/-2 状态。在一线治疗失败后，如果 ECOG 允许进一步治疗，应向患者提供二线治疗。在这里，5-FU/FA 加纳米脂质体伊立替康联合治疗在总生存期方面优于 5-FU/FA 单药治疗。免疫检查点抑制剂，如 PD1/PD-L1 mAbs，在高微卫星不稳定性（MSI-h）肿瘤中特别有效。在 mPDAC 中有限的数据表明，只有一小部分已经很小的 MSI-H mPDAC 亚组（频率约为 1%）似乎从检查点抑制剂治疗中获益显著。进一步确定亚组，例如具有 DNA 损伤修复缺陷、基因融合的肿瘤，以及肿瘤类器官指导治疗决策等新方法，可能会进一步提高治疗效果。
