Sorafenib in combination with erlotinib or with gemcitabine in elderly patients with advanced non-small-cell lung cancer: A randomized phase II study

C. Gridelli, F. Morgillo, A. Favaretto, F. de Marinis, A. Chella, G. Cerea, R. Mattioli, G. Tortora, A. Rossi, M. Fasano, G. Pasello, S. Ricciardi, P. Maione, M. di Maio, F. Ciardiello

Research output: Contribution to journalArticle

Abstract

Background: Sorafenib is a small-molecule multitargeted kinase inhibitor that blocks the activation of C-RAF, B-RAF, c-KIT, FLT-3, RET, vascular endothelial growth factor receptor 2 (VEGFR-2), VEGFR-3 and platelet-derived growth factor receptor β. The aim of this multicenter, randomized phase II study was to evaluate clinical activity and safety of sorafenib in combination with erlotinib or gemcitabine in unselected untreated elderly patients with non-small-cell lung cancer (NSCLC). Methods: The trial was designed to select the most promising sorafenib-containing combination in previously untreated elderly (≥70 years) stage IIIB or IV NSCLC patients, with performance status of zero to two. Patients were randomly assigned to one of the following combinations: gemcitabine, 1200 mg/m2 days 1 and 8, every 21 days, for a maximum of six cycles, plus sorafenib, 800 mg/day, until disease progression or unacceptable toxicity (arm 1); or erlotinib, 150 mg/day, plus sorafenib, 800 mg/day, until disease progression or unacceptable toxicity (arm 2). A selection design was applied with 1-year survival rate as the primary end point of the study, requiring 58 patients. Results: Sixty patients were randomly allocated to the study (31 patients in arm 1 and 29 patients in arm 2). After a median follow-up of 15 months, 10 patients [32%, 95% confidence interval (CI) 16% to 49%] in arm 1 and 13 patients (45%, 95% CI 27% to 63%) in arm 2 were alive at 1 year. Median overall survival was 6.6 and 12.6 months in arm 1 and arm 2, respectively. Observed toxic effects were consistent with the expected drug profiles. Conclusions: The combination of erlotinib and sorafenib was feasible in elderly patients with advanced NSCLC and was associated with a higher 1-year survival rate than the other arm. According to the selection design, this combination warrants further investigation in phase III trials.

Original languageEnglish
Pages (from-to)1528-1534
Number of pages7
JournalAnnals of Oncology
Volume22
Issue number7
DOIs
Publication statusPublished - 2011

Keywords

  • Elderly
  • Erlotinib
  • Gemcitabine
  • NSCLC
  • Sorafenib

ASJC Scopus subject areas

  • Oncology
  • Hematology

Fingerprint Dive into the research topics of 'Sorafenib in combination with erlotinib or with gemcitabine in elderly patients with advanced non-small-cell lung cancer: A randomized phase II study'. Together they form a unique fingerprint.

  • Cite this

    Gridelli, C., Morgillo, F., Favaretto, A., de Marinis, F., Chella, A., Cerea, G., Mattioli, R., Tortora, G., Rossi, A., Fasano, M., Pasello, G., Ricciardi, S., Maione, P., di Maio, M., & Ciardiello, F. (2011). Sorafenib in combination with erlotinib or with gemcitabine in elderly patients with advanced non-small-cell lung cancer: A randomized phase II study. Annals of Oncology, 22(7), 1528-1534. https://doi.org/10.1093/annonc/mdq630