Dual EGFR inhibition in combination with anti-VEGF treatment: A phase I clinical trial in non-small cell lung cancer

Gerald S. Falchook, Aung Naing, David S. Hong, Ralph Zinner, Siqing Fu, Sarina A. Piha-Paul, Apostolia M. Tsimberidou, Sonia K. Morgan-Linnell, Yunfang Jiang, Christel Bastida, Jennifer J. Wheler, Razelle Kurzrock

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Background: Preclinical data indicate EGFR signals through both kinasedependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic in animal models. Methods: We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with non-small cell lung cancer (NSCLC) was analyzed for safety and response. Results: Thirty-four patients with NSCLC (median four prior therapies) received treatment on a range of dose levels. The most common treatment-related grade =2 adverse events were rash (n=14, 41%), hypomagnesemia (n=9, 27%), and fatigue (n=5, 15%). Seven patients (21%) achieved stable disease (SD)≥6 months, two achieved a partial response (PR) (6%), and two achieved an unconfirmed partial response (uPR) (6%) (total=32%). We observed SD≥6 months/PR/uPR in patients who had received prior erlotinib and/or bevacizumab, those with brain metastases, smokers, and patients treated at lower dose levels. Five of 16 patients (31%) with wild-type EGFR experienced SD≥6 months or uPR. Correlation between grade of rash and rate of SD≥6 months/PR was observed (p<0.01). Conclusion: The combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC.

Original languageEnglish (US)
Pages (from-to)118-127
Number of pages10
JournalOncotarget
Volume4
Issue number1
DOIs
StatePublished - 2013

Keywords

  • Bevacizumab
  • Cetuximab
  • EGFR
  • Erlotinib
  • VEGF

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Dual EGFR inhibition in combination with anti-VEGF treatment: A phase I clinical trial in non-small cell lung cancer'. Together they form a unique fingerprint.

Cite this