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Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
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Are TKIs favourable for the elderly with non-small-cell lung cancer?

Sabrina Rossi1, Ettore D'Argento1, Giovanni Schinzari1

  • 1Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, Rome, Italy.

Oncotarget
|May 22, 2016
PubMed

Insights

Elderly patients with advanced non-small-cell lung cancer (NSCLC) and EGFR mutations showed better progression-free survival with Epidermal Growth Factor Receptor tyrosine-kinase inhibitors (TKIs). This suggests TKIs may be more effective in older populations.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Epidermal Growth Factor Receptor (EGFR) tyrosine-kinase inhibitors (TKIs) have transformed advanced non-small-cell lung cancer (NSCLC) treatment for patients with EGFR mutations.
  • This study retrospectively analyzed TKI efficacy and safety in elderly versus younger patients with advanced NSCLC.

Purpose of the Study:

  • To compare the efficacy and safety of first-line Epidermal Growth Factor Receptor tyrosine-kinase inhibitors (TKIs) in elderly (≥70 years) versus younger (<70 years) patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations.
  • To assess progression-free survival (PFS), response rate (RR), quality of life, and overall survival (OS).

Main Methods:

  • Retrospective analysis of 49 advanced NSCLC patients with EGFR exon 19 or 21 mutations receiving first-line TKIs.
  • Patients were divided into two groups: <70 years and ≥70 years.
  • Primary endpoints included PFS, RR, and quality of life; OS was a secondary endpoint.

Main Results:

  • Median PFS was significantly longer in elderly patients (12.6 months) compared to younger patients (5.6 months) (p=0.008).
  • The response rate (RR) was 75% in the elderly and 64% in younger patients.
  • Ninety percent of elderly patients on gefitinib experienced symptom relief and improved performance status. No significant difference in overall survival (OS) was observed (p=0.34).

Conclusions:

  • Epidermal Growth Factor Receptor tyrosine-kinase inhibitors (TKIs) appear more effective in elderly patients with EGFR-mutated non-small-cell lung cancer (NSCLC) compared to younger patients.
  • Hypothesized increased plasma TKI levels due to concomitant comorbidities in the elderly may contribute to enhanced efficacy.
Keywords:
Gerotargetafatinibconcomitant medicationsefficacyelderlygefitinib

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