Schlauch Daniel, Fu Xiaotong, Jones Suzanne F, Burris Howard A, Spigel David R, Reeves James, McKenzie Andrew J
Sarah Cannon Research Institute, Nashville, TN.
Genospace, Boston, MA.
JCO Precis Oncol. 2021 Nov;5:1625-1638. doi: 10.1200/PO.21.00008.
Next-generation sequencing (NGS) testing is being incorporated into routine standard of care for patients with cancer. Immune checkpoint inhibitors (CPIs) are approved for use in both tumor-specific and tumor-agnostic indications. We sought to determine tumor type-specific or tumor-agnostic correlations between mutations detected by NGS and response to CPIs.
A retrospective analysis of 26,004 patient records with NGS data available was conducted. Time to treatment failure and overall survival analyses were performed. Hazard ratios and associated statistics were computed in the R programming language. The study was considered exempt from internal review board review and data were considered nonhuman subjects.
Response to CPIs varied between tumor types with melanoma and lung cancer performing relatively better on CPIs than other tumor types. Within tumor types, response to CPIs was stratified by mutations in specific genes. Tumor-agnostic markers including high tumor mutation burden and microsatellite instability-high were also associated with longer time to treatment failure on CPIs. Importantly, within the high tumor mutation burden and microsatellite instability-high groups, mutations in individual genes correlate with response to CPIs.
The results from commercial NGS panels may be used to stratify patients for response to CPIs. In tumors where CPIs show relatively low efficacy, there may be distinct patient populations-based on gene mutation status-that are predicted to have better response to CPIs. Likewise, there may be distinct patient populations who do relatively worse on CPIs within tumor types known to respond well to CPIs.
下一代测序（NGS）检测正被纳入癌症患者的常规标准治疗中。免疫检查点抑制剂（CPI）已被批准用于肿瘤特异性和肿瘤非特异性适应症。我们试图确定通过NGS检测到的突变与对CPI反应之间的肿瘤类型特异性或肿瘤非特异性相关性。
对26,004份有NGS数据的患者记录进行回顾性分析。进行了治疗失败时间和总生存分析。在R编程语言中计算风险比和相关统计数据。该研究被认为无需内部审查委员会审查，数据被视为非人类受试者。
对CPI的反应在不同肿瘤类型之间存在差异，黑色素瘤和肺癌对CPI的反应相对优于其他肿瘤类型。在肿瘤类型内部，对CPI的反应按特定基因的突变进行分层。包括高肿瘤突变负荷和微卫星高度不稳定在内的肿瘤非特异性标志物也与CPI治疗失败时间延长相关。重要的是，在高肿瘤突变负荷和微卫星高度不稳定组中，单个基因的突变与对CPI的反应相关。
商业NGS检测结果可用于对患者对CPI的反应进行分层。在CPI疗效相对较低的肿瘤中，基于基因突变状态可能存在不同的患者群体，预计他们对CPI有更好的反应。同样，在已知对CPI反应良好的肿瘤类型中，可能也有对CPI反应相对较差的不同患者群体。
