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Successful Treatment of Afatinib-Refractory Non-Small Cell Lung Cancer with Uncommon Complex EGFR Mutations Using

Yuri Taniguchi1, Momoko Yamamoto1, Hiroaki Ikushima1

  • 1Division of Respirology, NTT Medical Center Tokyo, Tokyo, Japan.

Case Reports in Oncology
|August 21, 2019
PubMed

Insights

Immune-checkpoint inhibitors like pembrolizumab may benefit non-small cell lung cancer (NSCLC) patients with rare EGFR mutations who do not respond to targeted therapies. This case highlights a positive response to pembrolizumab after afatinib failure.

Area of Science:

  • Oncology
  • Immunotherapy
  • Genomics

Background:

  • Immune-checkpoint inhibitors (ICIs) are increasingly used in cancer treatment, but their role in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is debated.
  • EGFR-tyrosine kinase inhibitors (TKIs) are standard for EGFR-mutant NSCLC, but resistance and alternative treatment options are critical research areas.

Observation:

  • A 65-year-old female ex-smoker with stage IVB NSCLC presented with uncommon complex EGFR mutations (G719S and L861Q).
  • The patient showed rapid disease progression despite two months of afatinib treatment.
  • High PD-L1 expression (>75%) was detected in tumor cells, prompting pembrolizumab initiation.

Findings:

  • Pembrolizumab treatment led to a significant and durable response, remaining effective for over one year.
  • This indicates a potential benefit of ICIs in a subset of NSCLC patients with specific EGFR mutations.

Implications:

  • Pembrolizumab represents a viable treatment option for NSCLC patients with uncommon EGFR mutations refractory to EGFR-TKI therapy.
  • High PD-L1 expression may be a predictive biomarker for ICI response in this challenging patient population.
  • Further investigation into ICI efficacy in EGFR-mutant NSCLC with complex or rare mutations is warranted.
Keywords:
AfatinibEGFR uncommon mutationImmune-checkpoint inhibitorNon-small-cell lung cancerPembrolizumab

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