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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Response to Checkpoint Inhibition in Non-Small Cell Lung Cancer with Molecular Driver Alterations

Diego Kauffmann-Guerrero1, Amanda Tufman2, Kathrin Kahnert2

  • 1Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology Center Munich, University of Munich (LMU), Munich, Germany, Diego.KauffmannGuerrero@med.uni-muenchen.de.

Oncology Research and Treatment
|April 9, 2020
PubMed
Abstract

Insights

Immunotherapy response varies in non-small cell lung cancer (NSCLC) with driver mutations. KRAS, TP53, and MET exon 14 skipping mutations showed good responses, unlike PIK3CA, EGFR, and STK11 mutations.

Area of Science:

  • Oncology
  • Genomics
  • Immunotherapy

Background:

  • Checkpoint inhibitors show limited efficacy in EGFR-mutated non-small cell lung cancer (NSCLC).
  • Limited data exists on immunotherapy activity in NSCLC with diverse driver mutations.
  • Next-generation sequencing (NGS) identifies numerous driver mutations, complicating treatment selection.

Purpose of the Study:

  • To analyze immunotherapy response in NSCLC patients with various driver mutations.
  • To correlate molecular findings with treatment outcomes in NSCLC.
  • To evaluate the utility of molecular testing in guiding NSCLC immunotherapy decisions.

Main Methods:

  • Retrospective analysis of 84 NSCLC patients treated with immunotherapy at German centers.
  • Utilized next-generation sequencing (NGS) for molecular profiling.
  • Correlated immunotherapy response with identified driver mutations.

Main Results:

  • 51 patients had at least one driver mutation.
  • PIK3CA, EGFR, and STK11 mutations were associated with poor immunotherapy response.
  • KRAS, TP53, and MET exon 14 skipping mutations showed favorable responses.
  • One patient with an NF-1 mutation achieved a durable response.

Conclusions:

  • Molecular alterations significantly influence immunotherapy efficacy in NSCLC.
  • Specific driver mutations (KRAS, TP53, METex14) predict positive responses.
  • Molecular testing can aid in optimizing treatment strategies for NSCLC patients.
Keywords:
AtezolizumabEGFRKRASMETNivolumabNon-small cell lung cancerPIK3CAPembrolizumabSTK11TP53

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