Oncogene-specific differences in tumor mutational burden, PD-L1 expression, and outcomes from immunotherapy in non-small cell lung cancer.
Marcelo Vailati NegrãoFerdinandos SkoulidisMeagan MontesionKatja SchulzeIlze BaraVincent ShenHao XuSylvia HuDawen SuiYasir Y ElaminXiuning LeMichael E GoldbergKarthikeyan MurugesanChang-Jiun WuJianhua ZhangDavid S BarretoJacqulyne P RobichauxAlexandre ReubenTina CasconeCarl M GayKyle Gregory MitchellLingzhi HongWaree RinsurongkawongJack A RothStephen G SwisherJiun-Kae Jack LeeAnne TsaoVassiliki PapadimitrakopoulouDon L GibbonsBonnie S GlissonGaurav SingalVincent A MillerBrian AlexanderGarrett FramptonLee A AlbackerDavid ShamesJianjun ZhangJohn V HeymachPublished in: Journal for immunotherapy of cancer (2022)
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.