TY - JOUR
T1 - Dual EGFR inhibition in combination with anti-VEGF treatment
T2 - A phase I clinical trial in non-small cell lung cancer
AU - Falchook, Gerald S.
AU - Naing, Aung
AU - Hong, David S.
AU - Zinner, Ralph
AU - Fu, Siqing
AU - Piha-Paul, Sarina A.
AU - Tsimberidou, Apostolia M.
AU - Morgan-Linnell, Sonia K.
AU - Jiang, Yunfang
AU - Bastida, Christel
AU - Wheler, Jennifer J.
AU - Kurzrock, Razelle
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Bevacizumab
KW - Cetuximab
KW - EGFR
KW - Erlotinib
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=84875789255&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875789255&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.763
DO - 10.18632/oncotarget.763
M3 - Article
C2 - 23435217
AN - SCOPUS:84875789255
SN - 1949-2553
VL - 4
SP - 118
EP - 127
JO - Oncotarget
JF - Oncotarget
IS - 1
ER -