Multiple-line Chemotherapy and Tyrosine Kinase Inhibitor Treatment in Patients with Advanced Lung Cancer

Comb Chem High Throughput Screen. 2019;22(1):27-34. doi: 10.2174/1386207322666181231122030.

Abstract

Aim: To analyse the clinical outcomes of patients with lung cancer treated with first and multiple-line chemotherapy and tyrosine kinase inhibitor (TKI).

Patients & methods: The present study included a total of 89 patients of whom lung cancer was histologically confirmed between July 2016 and September 2017. Patients' demographics, chemotherapy/TKI treatment details and clinical outcomes were retrieved. The progression-free survivals (PFS) after first-line and multiple-line treatments were evaluated using Kaplan-Meier analysis with log-rank test. Risk factors for progressive disease (PD) were identified using Cox multivariate regression model.

Results: A total of 50 males and 39 females were enrolled. About 90% of the tumors were histologically classified as adenocarcinoma, and 77/89 cases (86.5%) were at TNM stage IV. The median PFS for the first-line treatment was 6.17 months. After first-line treatment, more favourable PFS was observed in patients who had prior surgery of lung cancer (P = 0.002). Multivariate analysis showed that patients who had received no prior surgical treatment for lung cancer were at higher risk of PD (OR, 4.311; 95% CI, 1.836 to 10.120; P = 0.0008). Besides, in patients with driver mutations, those who received no TKI treatment were under higher risk of PD compared to those who had been treated with TKI (OR, 4.876; 95% CI, 1.877 to 12.666; P = 0.0011). The median PFS for the multiple-line treatment was 24.67 months. After multiple-line treatments, favourable PFS was associated with tumor histological types of adenocarcinoma (P = 0.041), genetic lesions at exon 19 of EGFR (P = 0.001) and fourth-line treatment (P = 0.001). Risk factors for PD after multiple-line treatments were no prior surgery for lung cancer (OR, 3.335; 95% CI, 1.158 to 9.605; P = 0.0256), no TKI use in multiple-line treatment (OR, 10.095; 95% CI, 2.405 to 42.378; P = 0.0016), and being treated by first-line treatment alone (OR, 30.421; 95% CI, 4.813 to 192.269; P = 0.0003).

Conclusion: The present study demonstrated the benefits of TKI in patients with advanced lung cancer, providing insights into the refinement of the management strategy.

Keywords: Tyrosine kinase inhibitor (TKI); cancer management; chemotherapy; lung adenocarcinoma; progression-free survival; risk factor..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / chemistry
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Structure
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Retrospective Studies
  • Structure-Activity Relationship
  • Survival Analysis

Substances

  • Protein Kinase Inhibitors