Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Cancer Treat Rev. 2021 Dec;101:102310. doi: 10.1016/j.ctrv.2021.102310. Epub 2021 Oct 21.
Current guidelines recommend somatic genomic sequencing for patients with advanced pancreatic cancer to identify targetable alterations amenable to targeted therapy. The benefit of somatic genomic sequencing in pancreatic cancer remains unclear. This study aims to assess the evidence supporting genomic sequencing to inform treatment selection for patients with advanced pancreatic cancer.
A systematic review identified prospective studies of exocrine pancreatic cancer patients published before August 2020 which conducted genomic sequencing to inform treatment selection. Outcomes of interest included the proportion of patients with targetable alterations, the proportion that received targeted treatments, and the impact of targeted treatments on overall survival. Meta-analysis for proportions and hazard ratios was performed using Dersimonian and Laird random effect models.
19 studies (representing 2048 pancreatic cancer patients) were included. Sequencing methodologies, definitions of targetable alterations, and approaches treatment selection varied across studies and were incompletely reported. 590 of 1382 sequenced patients harboured a targetable alteration (random effects meta-analysis estimate of the proportion 0.46, 95% confidence interval 0.32-0.61). The proportion of patients with targetable alterations was highly heterogenous between studies (I 93%, P < 0.001). 91 of 1390 patients received a matched therapy based on their targetable alterations (random effects meta-analysis estimate of the proportion 0.12, 95% CI 0.06-0.23). One observational study reported an overall survival benefit of matched therapy.
Genomic sequencing frequently identifies targetable alterations in pancreatic cancers. Further research is required to standardize the definitions of targetable alterations, the approach to treatment matching, and quantify the benefit of targeted therapy.
目前的指南建议对晚期胰腺癌患者进行体细胞基因组测序，以确定可通过靶向治疗来改善的可靶向改变。基因组测序在胰腺癌中的获益仍不明确。本研究旨在评估支持基因组测序以告知晚期胰腺癌患者治疗选择的证据。
系统回顾确定了 2020 年 8 月前发表的、对接受基因组测序以指导治疗选择的外分泌胰腺癌细胞患者进行的前瞻性研究。感兴趣的结局包括具有可靶向改变的患者比例、接受靶向治疗的患者比例以及靶向治疗对总生存的影响。使用 Dersimonian 和 Laird 随机效应模型对比例和风险比进行荟萃分析。
共纳入 19 项研究（代表 2048 例胰腺癌患者）。测序方法、可靶向改变的定义以及治疗选择方法在不同研究中存在差异，且报道不完整。在 1382 例测序患者中，590 例（随机效应荟萃分析估计的比例为 0.46，95%置信区间为 0.32-0.61）存在可靶向改变。研究之间具有高度异质性（I 93%，P < 0.001）。在 1390 例患者中，有 91 例根据其可靶向改变接受了匹配治疗（随机效应荟萃分析估计的比例为 0.12，95%置信区间为 0.06-0.23）。一项观察性研究报告称匹配治疗具有总生存获益。
基因组测序经常可识别出胰腺癌中的可靶向改变。需要进一步的研究来标准化可靶向改变的定义、治疗匹配方法，并量化靶向治疗的获益。
