Impact of Epidermal Growth Factor Receptor Mutation on Clinical Outcomes of Nintedanib Plus Docetaxel in Patients with Previously Treated Non-Small Cell Lung Cancer from the Korean Named Patient Program

Oncology. 2019;96(1):51-58. doi: 10.1159/000492472. Epub 2018 Oct 26.

Abstract

Objectives: Anti-angiogenic agents are reported to exert clinical activity on epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancers. We evaluated the clinical outcomes of nintedanib and docetaxel in refractory NSCLC according to EGFR mutation status during the Korean nintedanib named patient program.

Methods: Docetaxel was administered either 75 or 37.5 mg/m2 on D1, D8 q every 3 weeks for 4-6 cycles plus nintedanib 200 mg orally twice daily until disease progression or unacceptable toxicity.

Results: Sixty-two patients were enrolled for study. Twenty-eight patients with activating EGFR mutations progressed after EGFR-tyrosine kinase inhibitors (TKI) therapy and 25 out of 28 patients showing progression after platinum doublet chemotherapy were enrolled. The objective response rate was 29% and median PFS and OS were 3.9 months and 11.7 months. Based on the EGFR mutation status, the objective response rate was 39.3 vs. 21.9% (EGFR mut(+) vs. EGFR mut(-), p = 0.142) and median PFS was 6.5 vs. 3.3 months (EGFR mut(+) vs. EGFR mut(-), p = 0.009). No treatment-related deaths were reported. The most frequent drug-related adverse events (AE) were neutropenia (53.2%) and diarrhea (37.1%). Treatment in 12 patients (19.3%) was permanently discontinued due to AEs without disease progression.

Conclusions: Our data indicated that nintedanib-docetaxel combination could be considered to be effective treatment in EGFR TKI-resistant EGFR mutant NSCLC.

Keywords: Docetaxel; Epidermal growth factor receptor; Nintedanib; Non-small-cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Combined Modality Therapy
  • Docetaxel / administration & dosage
  • Drug Resistance, Neoplasm
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Indoles / administration & dosage
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Prognosis
  • Retreatment
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Indoles
  • Docetaxel
  • ErbB Receptors
  • nintedanib