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.

Limitations

  • 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.

Disclosures

  • 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 The study has not been peer-reviewed can be found at medrxiv.org.

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: aotto@mdedge.com

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