BE-POSITIVE: Beyond progression after tyrosine kinase inhibitor in EGFR- positive non small cell lung cancer patients: Results from a multicenter Italian observational study

Lung Cancer. 2016 May:95:73-81. doi: 10.1016/j.lungcan.2016.02.011. Epub 2016 Feb 26.

Abstract

Objectives: Non-small-cell-lung-cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations develop drug resistance after 9-12 months of EGFR tyrosine kinase inhibitors (TKIs) therapy pointing out the issue of the second-line treatment choice.

Materials and methods: From June 2009 until May 2013 patients affected by advanced NSCLC harbouring EGFR mutations receiving first-line TKI were collected mainly retrospectively in 24 Italian Centers. Primary objective was to describe the percentage of EGFR mutated patients receiving second-line therapy after progression to first-line EGFR-TKIs assessing the type, the activity in terms of objective response rate (ORR), efficacy in terms of progression free survival (PFS) and overall survival (OS), and safety of second-line treatment. Secondary objective was to describe the efficacy of first-line EGFR-TKIs.

Results: 312 patients were included. Most of them were females (203, 65.1%), never smokers (200, 64.1%), with adenocarcinoma histology (290, 92.9%). The most common mutations were EGFR exon 19 deletion and L858R, detected in 186 and 97 cases (59.6% and 31.1%), respectively. At data cut-off, 274 patients (95.1%) received any second-line treatment (including best supportive care or local treatments only). A total of 163 patients received second-line systemic therapy with an ORR of 20.9% (95% CI:14.62-27.10), a median PFS and OS of 4.7 (95% CI:3.81-5.26) and 24.5 (95% CI:21.65-27.37) months, respectively. Grade 3-4 hematological and non-hematological toxicities were reported in 9% and 6.3% of 144 patients treated with chemotherapy while non-hematological toxicity was reported in 4 cases of the 17 patients receiving second-line target agents.

Conclusions: BE-Positive is the first multicenter observational study reporting outcomes of therapies in a "real-life Caucasian EGFR-mutated population", highlighting the need of further researches about new treatment strategies in this setting.

Keywords: Acquired resistance; EGFR mutation; EGFR tyrosine kinase inhibitors; First line; Non small cell lung cancer; Second line.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • 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
  • Disease Progression
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Italy
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Retreatment
  • Risk Factors
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • ErbB Receptors