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Optimal Management of Patients with Advanced NSCLC Harboring High PD-L1 Expression and Driver Mutations

  • Lung Cancer (HA Wakelee and TA Leal, Section Editors)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Patients with stage IV or recurrent/metastatic non-small cell lung cancer (NSCLC) whose tumors harbor high PD-L1 expression and driver mutations with approved targeted treatments (EGFR, ALK, BRAFV600E, ROS1) should receive initial therapy with targeted therapy based on impressive clinical activity. PD-(L)1 inhibitors have demonstrated minimal activity in many driver mutation subsets including EGFR and ALK and appears to have more benefit in smoking-associated oncogenic drivers (KRAS, BRAF). For KRAS-driven tumors, co-mutations such as STK11/LKB1 are negative predictive markers of immunotherapy with or without chemotherapy. Therefore, driver mutations need to be evaluated before pursuing immunotherapy independent of PD-L1 expression level. Caution should be used with TKIs following or concurrent with immunotherapy owing to potentially increased toxicity. New immunotherapy combinations are needed especially for oncogene-driven tumors associated with never or light smoking history.

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  1. Department of Internal Medicine, Division of Hematology and Oncology, UC Davis Comprehensive Cancer Center, 4501 X St, Suite 3016, Sacramento, CA, 95817, USA

    Justin A. Chen MD & Jonathan W. Riess MD MS

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Correspondence to Justin A. Chen MD.

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Justin A. Chen receives AACR-AstraZeneca grant support (starting July 2020); and Jonathan W. Riess has received research funding (paid to his institution) from Boehringer Ingelheim, Merck, Novartis, and AstraZeneca; has received honoraria for service on advisory boards from Celgene, Heron, Takeda, AbbVie, Boehringer Ingelhim, Loxo Oncology, Spectrum, and Medtronic, and received compensation for service as a consultant from Celgene.

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Chen, J.A., Riess, J.W. Optimal Management of Patients with Advanced NSCLC Harboring High PD-L1 Expression and Driver Mutations. Curr. Treat. Options in Oncol. 21, 60 (2020). https://doi.org/10.1007/s11864-020-00750-y

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