Key Takeaway
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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
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Pembrolizumab is a first-line immunotherapy indicated for metastatic NSCLC.
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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.
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The new findings address an unmet need to better stratify pembrolizumab responders from nonresponders.
Study Design
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The study was a review of 580 Swedish patients with metastatic NSCLC diagnosed between 2016 and 2018.
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The aim was to determine the impact of the KRAS mutation and PD-L1 expression on survival after first-line treatment.
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During the study period, pembrolizumab was the only immune checkpoint inhibitor approved for NSCLC.
Key Findings
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36% of patients had a KRAS mutation.
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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).
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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.
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No correlation was found between PD-L1 expression and overall survival with wild-type KRAS.
Limitations
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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.
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The impact of co-mutations on immune checkpoint blockade efficacy was not assessed.
Disclosures
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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