KRAS Mutation Predicts Pembrolizumab Response in NSCLC

December 02, 2021

Key Takeaway

  • KRAS mutation in combination with high PD-L1 expression (≥ 50%) is better than high PD-L1 alone at predicting response to first-line pembrolizumab in patients with metastatic nonsmall cell lung cancer (NSCLC). 

Why This Matters

  • Pembrolizumab is a first-line immunotherapy indicated for metastatic NSCLC.

  • PD-L1 expression is used to predict who will respond to the drug and select patients for treatment; however, it's not a reliable method.

  • The new findings address an unmet need to better stratify pembrolizumab responders from nonresponders.

Study Design

  • The study was a review of 580 Swedish patients with metastatic NSCLC diagnosed between 2016 and 2018.

  • The aim was to determine the impact of the KRAS mutation and PD-L1 expression on survival after first-line treatment.

  • During the study period, pembrolizumab was the only immune checkpoint inhibitor approved for NSCLC.

Key Findings

  • 36% of patients had a KRAS mutation.

  • Patients with a KRAS mutation who received pembrolizumab had significantly better median overall survival compared to patients with wild-type KRAS (23 vs 6 months, respectively; P = .006).

  • Patients harboring a KRAS mutation varied in terms of overall survival according to PD-L1 expression, with an overall survival of 6 months among non-expressors, 11 months among low expressors, and 17 months among high expressors.

  • No correlation was found between PD-L1 expression and overall survival with wild-type KRAS.


  • A relatively small number of patients were treated with first-line immune checkpoint blockade therapy during the study, so the findings must be confirmed in larger studies.

  • The impact of co-mutations on immune checkpoint blockade efficacy was not assessed.


  • The study was supported by the Swedish Society for Medical Research and others.

  • The authors had no conflicts of interest.

This is a summary of a preprint research report led by Ella Eklund of the University of Gothenburg, Sweden, provided to you by Medscape. The study has not been peer-reviewed can be found at

M. Alexander Otto is a physician assistant with a master's degree in medical science and an award-winning medical journalist who has worked for several major news outlets before joining Medscape. He is an MIT Knight Science Journalism fellow. Email:

Follow Medscape on Facebook, Twitter, Instagram, and YouTube.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.