Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs

Anticancer Res. 2018 Aug;38(8):4699-4704. doi: 10.21873/anticanres.12776.

Abstract

Background/aim: Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed.

Patients and methods: We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs.

Results: Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2). Dose-limiting toxicities included delay of afatinib ≥14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression-free survival was 13.7 months.

Conclusion: This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy.

Keywords: Afatinib; EGFR mutation; carboplatin; non-small-cell lung cancer; pemetrexed.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Afatinib
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / therapeutic use
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Disease-Free Survival
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation / genetics
  • Organoplatinum Compounds / therapeutic use
  • Pemetrexed / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / administration & dosage
  • Treatment Outcome
  • Young Adult

Substances

  • Organoplatinum Compounds
  • Protein Kinase Inhibitors
  • Quinazolines
  • Pemetrexed
  • Bevacizumab
  • Afatinib
  • Carboplatin
  • EGFR protein, human
  • ErbB Receptors