Dual EGFR inhibition in combination with anti-VEGF treatment: a phase I clinical trial in non-small cell lung cancer. Oncotarget 2013 Jan;4(1):118-27
Date
02/26/2013Pubmed ID
23435217Pubmed Central ID
PMC3702212DOI
10.18632/oncotarget.763Scopus ID
2-s2.0-84875789255 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
BACKGROUND: Preclinical data indicate EGFR signals through both kinase-dependent 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 less than 0.01).
CONCLUSION: The combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC.
Author List
Falchook GS, Naing A, Hong DS, Zinner R, Fu S, Piha-Paul SA, Tsimberidou AM, Morgan-Linnell SK, Jiang Y, Bastida C, Wheler JJ, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Bevacizumab
Carcinoma, Non-Small-Cell Lung
Cetuximab
Dose-Response Relationship, Drug
ErbB Receptors
Erlotinib Hydrochloride
Exanthema
Fatigue
Female
Genotype
Humans
Lung Neoplasms
Male
Middle Aged
Quinazolines
Treatment Outcome
Vascular Endothelial Growth Factor A
