The Impact of EGFR Mutation Status and Brain Metastasis for Non-Small Cell Lung Cancer Treated with Ramucirumab plus Docetaxel

Oncology. 2020;98(9):661-668. doi: 10.1159/000507050. Epub 2020 May 28.

Abstract

Objectives: Currently, combination therapy of ramucirumab (RAM) + docetaxel (DOC) must play a more important role as a second-line treatment. Epithelial growth factor receptor (EGFR) mutation accounts for around 50% of oncogenic driver mutations in patients with advanced non-small cell lung cancer (NSCLC) in Asian subsets. The number of brain metastases (BM) is relatively higher in EGFR mutation-positive patients compared to EGFR wild-type patients. The objective of this study is to evaluate the efficacy of RAM + DOC focusing on EGFR mutation and BM.

Methods: We retrospectively reviewed consecutive advanced NSCLC patients who received combination therapy of RAM + DOC at three institutions. A total of 112 patients with NSCLC were enrolled for efficacy analyses. We evaluated the efficacy of RAM + DOC for EGFR-mutated NSCLC with endpoints including progression-free survival (PFS), time to treatment failure (TTF) and overall survival.

Results: Median PFS was 5.7 months for the EGFR mutant group compared with 3.6 months for the EGFR wild-type group (HR 0.53, 95% CI 0.32-0.87; p = 0.01). Median TTF was 5.1 months for the EGFR mutant group compared with 2.8 months for the EGFR wild-type group (HR 0.53, 95% CI 0.33-0.85; p = 0.007). Median PFS and TTF of the EGFR mutant group was significantly longer than median PFS and TTF of the EGFR wild-type group. The multivariate analysis identified EGFR mutation status as an independent favorable factor of PFS. In subset analyses of BM, median PFS of the EGFR mutant group (2.8 months) was significantly shorter than that of the EGFR wild-type group (5.1 months) (HR 7.27, 95% CI 1.78-29.68; p = 0.002).

Conclusion: This study revealed that EGFR mutation status and BM might be predictive or prognostic factors for PFS.

Keywords: Brain metastasis; Docetaxel; EGFR mutation; Non-small cell lung cancer; Ramucirumab.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Docetaxel / administration & dosage
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Progression-Free Survival
  • Ramucirumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Docetaxel
  • EGFR protein, human
  • ErbB Receptors