1. Dual EGFR inhibition in combination with anti-VEGF treatment: A phase I clinical trial in non-small cell lung cancer
- Author
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Falchook, Gerald S, Naing, Aung, Hong, David S, Zinner, Ralph, Fu, Siqing, Piha-Paul, Sarina A, Tsimberidou, Apostolia M, Morgan-Linnell, Sonia K, Jiang, Yunfang, Bastida, Christel, Wheler, Jennifer J, and Kurzrock, Razelle
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Clinical Research ,Lung Cancer ,Lung ,6.2 Cellular and gene therapies ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Aged ,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 ,Erlotinib ,EGFR ,VEGF ,Oncology and carcinogenesis - Abstract
BackgroundPreclinical 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.MethodsWe 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.ResultsThirty-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).ConclusionThe combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC.
- Published
- 2013