Non-small cell lung cancer (NSCLC) patients bearing targetable oncogene alterations typically derive limited benefit from immune checkpoint blockade (ICB), which has been attributed to low tumor mutation burden (TMB) and/or PD-L1 levels. We investigated oncogene-specific differences in these markers and clinical outcome.
We concluded that high TMB and PD-L1 expression are predictive for benefit from ICB treatment in oncogene-driven NSCLCs. NSCLC harboring BRAF mutations demonstrated superior benefit from ICB that may be attributed to higher TMB and higher PD-L1 expression in these tumors. Meanwhile EGFR and HER2 mutations and ALK, ROS1, RET, and MET fusions define NSCLC subsets with minimal benefit from ICB despite high PD-L1 expression in NSCLC harboring oncogene fusions. These findings indicate a TMB/PD-L1-independent impact on sensitivity to ICB for certain oncogene alterations. READ ARTICLE
Journal for ImmunoTherapy of Cancer DOI:10.1136/jitc-2021-002891
Authors: Marcelo V Negrao, Ferdinandos Skoulidis, Meagan Montesion, Katja Schulze, Ilze Bara, Vincent Shen, Hao Xu, Sylvia Hu, Dawen Sui, Yasir Y Elamin, Xiuning Le, Michael E Goldberg, Karthikeyan Murugesan, Chang-Jiun Wu, Jianhua Zhang, David S Barreto, Jacqulyne P Robichaux, Alexandre Reuben, Tina Cascone, Carl M Gay, Kyle G Mitchell, Lingzhi Hong, Waree Rinsurongkawong, Jack A Roth, Stephen G Swisher, Jack Lee, Anne Tsao, Vassiliki Papadimitrakopoulou, Don L Gibbons, Bonnie S Glisson, Gaurav Singal, Vincent A Miller, Brian Alexander, Garrett Frampton, Lee A Albacker, David Shames, Jianjun Zhang, and John V Heymach