Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer.

Roy S. Herbst, David H. Johnson, Eric Mininberg, David P. Carbone, Ted Henderson, Edward S. Kim, George Blumenschein, Jack J. Lee, Diane D. Liu, Mylene T. Truong, Waun K. Hong, Hai Tran, Anne Tsao, Dong Xie, David A. Ramies, Robert Mass, Somasekar Seshagiri, David A. Eberhard, Sean K. Kelley, Alan Sandler

Research output: Contribution to journalArticle

500 Citations (Scopus)

Abstract

PURPOSE: Bevacizumab (Avastin; Genentech, South San Francisco, CA) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody. Erlotinib HCl (Tarceva, OSI-774; OSI Pharmaceuticals, New York, NY) is a potent, reversible, highly selective and orally available HER-1/epidermal growth factor receptor tyrosine kinase inhibitor. Preclinical data in various xenograft models produced greater growth inhibition than with either agent alone. Additionally, both agents have demonstrated benefit in patients with previously treated non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A phase I/II study in two centers examined erlotinib and bevacizumab (A+T) in patients with nonsquamous stage IIIB/IV NSCLC with > or = one prior chemotherapy. In phase I, erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days was established as the phase II dose, although no dose-limiting toxicities were observed. Phase II assessed the efficacy and tolerability of A+T at this dose. Pharmacokinetic parameters were evaluated.ResultsForty patients were enrolled and treated in this study (34 patients at phase II dose); the median age was 59 years (range, 36 to 72 years), 21 were female, 30 had adenocarcinoma histology, nine were never-smokers, and 22 had > or = two prior regimens (three patients had > or = four prior regimens). The most common adverse events were mild to moderate rash, diarrhea, and proteinuria. Preliminary data showed no pharmacokinetic interaction between A + T. Eight patients (20.0%; 95% CI, 7.6% to 32.4%) had partial responses and 26 (65.0%; 95% CI, 50.2% to 79.8%) had stable disease as their best response. The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months. CONCLUSION: Encouraging antitumor activity and safety of A + T support further development of this combination for patients with advanced NSCLC and other solid tumors.

Original languageEnglish (US)
Pages (from-to)2544-2555
Number of pages12
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume23
Issue number11
StatePublished - Apr 10 2005

Fingerprint

Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
Monoclonal Antibodies
Pharmacokinetics
Erlotinib Hydrochloride
Bevacizumab
San Francisco
Exanthema
Proteinuria
Heterografts
Disease-Free Survival
Diarrhea
Histology
Adenocarcinoma
Safety
Drug Therapy
Survival
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. / Herbst, Roy S.; Johnson, David H.; Mininberg, Eric; Carbone, David P.; Henderson, Ted; Kim, Edward S.; Blumenschein, George; Lee, Jack J.; Liu, Diane D.; Truong, Mylene T.; Hong, Waun K.; Tran, Hai; Tsao, Anne; Xie, Dong; Ramies, David A.; Mass, Robert; Seshagiri, Somasekar; Eberhard, David A.; Kelley, Sean K.; Sandler, Alan.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 23, No. 11, 10.04.2005, p. 2544-2555.

Research output: Contribution to journalArticle

Herbst, RS, Johnson, DH, Mininberg, E, Carbone, DP, Henderson, T, Kim, ES, Blumenschein, G, Lee, JJ, Liu, DD, Truong, MT, Hong, WK, Tran, H, Tsao, A, Xie, D, Ramies, DA, Mass, R, Seshagiri, S, Eberhard, DA, Kelley, SK & Sandler, A 2005, 'Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer.', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 23, no. 11, pp. 2544-2555.
Herbst, Roy S. ; Johnson, David H. ; Mininberg, Eric ; Carbone, David P. ; Henderson, Ted ; Kim, Edward S. ; Blumenschein, George ; Lee, Jack J. ; Liu, Diane D. ; Truong, Mylene T. ; Hong, Waun K. ; Tran, Hai ; Tsao, Anne ; Xie, Dong ; Ramies, David A. ; Mass, Robert ; Seshagiri, Somasekar ; Eberhard, David A. ; Kelley, Sean K. ; Sandler, Alan. / Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005 ; Vol. 23, No. 11. pp. 2544-2555.
@article{a998bbd8a91f4caaa9c13f2297d31a5d,
title = "Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer.",
abstract = "PURPOSE: Bevacizumab (Avastin; Genentech, South San Francisco, CA) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody. Erlotinib HCl (Tarceva, OSI-774; OSI Pharmaceuticals, New York, NY) is a potent, reversible, highly selective and orally available HER-1/epidermal growth factor receptor tyrosine kinase inhibitor. Preclinical data in various xenograft models produced greater growth inhibition than with either agent alone. Additionally, both agents have demonstrated benefit in patients with previously treated non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A phase I/II study in two centers examined erlotinib and bevacizumab (A+T) in patients with nonsquamous stage IIIB/IV NSCLC with > or = one prior chemotherapy. In phase I, erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days was established as the phase II dose, although no dose-limiting toxicities were observed. Phase II assessed the efficacy and tolerability of A+T at this dose. Pharmacokinetic parameters were evaluated.ResultsForty patients were enrolled and treated in this study (34 patients at phase II dose); the median age was 59 years (range, 36 to 72 years), 21 were female, 30 had adenocarcinoma histology, nine were never-smokers, and 22 had > or = two prior regimens (three patients had > or = four prior regimens). The most common adverse events were mild to moderate rash, diarrhea, and proteinuria. Preliminary data showed no pharmacokinetic interaction between A + T. Eight patients (20.0{\%}; 95{\%} CI, 7.6{\%} to 32.4{\%}) had partial responses and 26 (65.0{\%}; 95{\%} CI, 50.2{\%} to 79.8{\%}) had stable disease as their best response. The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months. CONCLUSION: Encouraging antitumor activity and safety of A + T support further development of this combination for patients with advanced NSCLC and other solid tumors.",
author = "Herbst, {Roy S.} and Johnson, {David H.} and Eric Mininberg and Carbone, {David P.} and Ted Henderson and Kim, {Edward S.} and George Blumenschein and Lee, {Jack J.} and Liu, {Diane D.} and Truong, {Mylene T.} and Hong, {Waun K.} and Hai Tran and Anne Tsao and Dong Xie and Ramies, {David A.} and Robert Mass and Somasekar Seshagiri and Eberhard, {David A.} and Kelley, {Sean K.} and Alan Sandler",
year = "2005",
month = "4",
day = "10",
language = "English (US)",
volume = "23",
pages = "2544--2555",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "11",

}

TY - JOUR

T1 - Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer.

AU - Herbst, Roy S.

AU - Johnson, David H.

AU - Mininberg, Eric

AU - Carbone, David P.

AU - Henderson, Ted

AU - Kim, Edward S.

AU - Blumenschein, George

AU - Lee, Jack J.

AU - Liu, Diane D.

AU - Truong, Mylene T.

AU - Hong, Waun K.

AU - Tran, Hai

AU - Tsao, Anne

AU - Xie, Dong

AU - Ramies, David A.

AU - Mass, Robert

AU - Seshagiri, Somasekar

AU - Eberhard, David A.

AU - Kelley, Sean K.

AU - Sandler, Alan

PY - 2005/4/10

Y1 - 2005/4/10

N2 - PURPOSE: Bevacizumab (Avastin; Genentech, South San Francisco, CA) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody. Erlotinib HCl (Tarceva, OSI-774; OSI Pharmaceuticals, New York, NY) is a potent, reversible, highly selective and orally available HER-1/epidermal growth factor receptor tyrosine kinase inhibitor. Preclinical data in various xenograft models produced greater growth inhibition than with either agent alone. Additionally, both agents have demonstrated benefit in patients with previously treated non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A phase I/II study in two centers examined erlotinib and bevacizumab (A+T) in patients with nonsquamous stage IIIB/IV NSCLC with > or = one prior chemotherapy. In phase I, erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days was established as the phase II dose, although no dose-limiting toxicities were observed. Phase II assessed the efficacy and tolerability of A+T at this dose. Pharmacokinetic parameters were evaluated.ResultsForty patients were enrolled and treated in this study (34 patients at phase II dose); the median age was 59 years (range, 36 to 72 years), 21 were female, 30 had adenocarcinoma histology, nine were never-smokers, and 22 had > or = two prior regimens (three patients had > or = four prior regimens). The most common adverse events were mild to moderate rash, diarrhea, and proteinuria. Preliminary data showed no pharmacokinetic interaction between A + T. Eight patients (20.0%; 95% CI, 7.6% to 32.4%) had partial responses and 26 (65.0%; 95% CI, 50.2% to 79.8%) had stable disease as their best response. The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months. CONCLUSION: Encouraging antitumor activity and safety of A + T support further development of this combination for patients with advanced NSCLC and other solid tumors.

AB - PURPOSE: Bevacizumab (Avastin; Genentech, South San Francisco, CA) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody. Erlotinib HCl (Tarceva, OSI-774; OSI Pharmaceuticals, New York, NY) is a potent, reversible, highly selective and orally available HER-1/epidermal growth factor receptor tyrosine kinase inhibitor. Preclinical data in various xenograft models produced greater growth inhibition than with either agent alone. Additionally, both agents have demonstrated benefit in patients with previously treated non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A phase I/II study in two centers examined erlotinib and bevacizumab (A+T) in patients with nonsquamous stage IIIB/IV NSCLC with > or = one prior chemotherapy. In phase I, erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days was established as the phase II dose, although no dose-limiting toxicities were observed. Phase II assessed the efficacy and tolerability of A+T at this dose. Pharmacokinetic parameters were evaluated.ResultsForty patients were enrolled and treated in this study (34 patients at phase II dose); the median age was 59 years (range, 36 to 72 years), 21 were female, 30 had adenocarcinoma histology, nine were never-smokers, and 22 had > or = two prior regimens (three patients had > or = four prior regimens). The most common adverse events were mild to moderate rash, diarrhea, and proteinuria. Preliminary data showed no pharmacokinetic interaction between A + T. Eight patients (20.0%; 95% CI, 7.6% to 32.4%) had partial responses and 26 (65.0%; 95% CI, 50.2% to 79.8%) had stable disease as their best response. The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months. CONCLUSION: Encouraging antitumor activity and safety of A + T support further development of this combination for patients with advanced NSCLC and other solid tumors.

UR - http://www.scopus.com/inward/record.url?scp=20244381389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20244381389&partnerID=8YFLogxK

M3 - Article

VL - 23

SP - 2544

EP - 2555

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 11

ER -