A phase 2 study of bevacizumab in combination with carboplatin and paclitaxel in patients with non-squamous non-small-cell lung cancer harboring mutations of epidermal growth factor receptor (EGFR) after failing first-line EGFR-tyrosine kinase inhibitors (HANSHIN Oncology Group 0109)

Lung Cancer. 2015 Feb;87(2):136-40. doi: 10.1016/j.lungcan.2014.12.007. Epub 2014 Dec 19.

Abstract

Objectives: We have conducted a phase 2 study to evaluate the efficacy and safety of carboplatin, paclitaxel, and bevacizumab in patients with non-squamous non-small-cell lung cancer (NSCLC) who are epidermal growth factor receptor (EGFR) mutation positive and for whom EGFR-tyrosine kinase inhibitor (TKI) 1st-line has failed.

Materials and methods: Patients with stage IIIB or IV non-squamous NSCLC harbored activating EGFR mutations that has failed 1st-line EGFR-TKI and an Eastern Cooperative Oncology Group performance status of 0 or 1 were included in this study. Patients received carboplatin at an area under the concentration-time curve 5 or 6, paclitaxel 200mg/m(2), and bevacizumab 15mg/kg on D1. The combination therapy was repeated every 21 days for up to three to six cycles. Bevacizumab was continued until disease progression or unacceptable toxicity for patients without disease progression (PD). The primary endpoint was objective response rate (ORR).

Results: Thirty-one patients were enrolled between March 2010 and January 2013, with 30 patients being eligible. ORR was 37% (90% CI; 24-52%) and disease control rate, 83% (95% CI; 66-92%). The median progression free survival (PFS) was 6.6 months (95% CI; 4.8-12.0 months) and median overall survival, 18.2 months (95% CI; 12.0-23.4 months). The most common grade ≥3 hematologic toxicity was neutropenia (93%), and non-hematologic toxicity, febrile neutropenia (20%). There were no clinically relevant grade ≥3 bleeding events and no treatment-related deaths.

Conclusion: The combination therapy of carboplatin, paclitaxel and bevacizumab did not achieve the initial treatment goal.

Keywords: Bevacizumab; Carboplatin; Epidermal growth factor receptor mutation; Non-small-cell lung cancer; Paclitaxel; Second-line.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Progression
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Recurrence
  • Retreatment
  • Risk Factors
  • Treatment Failure
  • Treatment Outcome

Substances

  • Bevacizumab
  • Carboplatin
  • EGFR protein, human
  • ErbB Receptors
  • Paclitaxel