Originally published as JCO Early Release 10.1200/JCO.2007.12.3026 on October 1 2007
Journal of Clinical Oncology, Vol 25, No 30 (October 20), 2007: pp. 4743-4750
© 2007 American Society of Clinical Oncology.
Phase II Study of Efficacy and Safety of Bevacizumab in Combination With Chemotherapy or Erlotinib Compared With Chemotherapy Alone for Treatment of Recurrent or Refractory Non–Small-Cell Lung Cancer
Roy S. Herbst,
Vincent J. O'Neill,
Louis Fehrenbacher,
Chandra P. Belani,
Philip D. Bonomi,
Lowell Hart,
Ostap Melnyk,
David Ramies,
Ming Lin,
Alan Sandler
From The M.D. Anderson Cancer Center, Houston, TX; Genentech Inc, South San Francisco; Kaiser Permanente Northern California, Vallejo; Bay Area Cancer Research Group, Concord, CA; University of Pittsburgh Cancer Institute, Pittsburgh, PA; Rush University Medical Center, Chicago, IL; Florida Cancer Specialists, Ft Meyers, FL; and Vanderbilt University, Nashville, TN
Address reprint requests to Roy S. Herbst, MD, PhD, The M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX 77030; e-mail: rherbst{at}mdanderson.org
Purpose Bevacizumab, a humanized anti–vascular endothelial growth factor monoclonal antibody, and erlotinib, a reversible, orally available epidermal growth factor receptor tyrosine kinase inhibitor, have demonstrated evidence of a survival benefit in the treatment of non–small-cell lung cancer (NSCLC). A single-arm phase I and II study of bevacizumab plus erlotinib demonstrated encouraging efficacy, with a favorable safety profile.
Patients and Methods A multicenter, randomized phase II trial evaluated the safety of combining bevacizumab with either chemotherapy (docetaxel or pemetrexed) or erlotinib and preliminarily assessed these combinations versus chemotherapy alone, as measured by progression-free survival (PFS). All patients had histologically confirmed nonsquamous NSCLC that had progressed during or after one platinum-based regimen.
Results One hundred twenty patients were randomly assigned and treated. No unexpected adverse events were noted. Fewer patients (13%) in the bevacizumab-erlotinib arm discontinued treatment as a result of adverse events than in the chemotherapy alone (24%) or bevacizumab-chemotherapy (28%) arms. The incidence of grade 5 hemorrhage in patients receiving bevacizumab was 5.1%. Although not statistically significant, relative to chemotherapy alone, the risk of disease progression or death was 0.66 (95% CI, 0.38 to 1.16) among patients treated with bevacizumab-chemotherapy and 0.72 (95% CI, 0.42 to 1.23) among patients treated with bevacizumab-erlotinib. One-year survival rate was 57.4% for bevacizumab-erlotinib and 53.8% for bevacizumab-chemotherapy compared with 33.1% for chemotherapy alone.
Conclusion Results for PFS and overall survival favor combination of bevacizumab with either chemotherapy or erlotinib over chemotherapy alone in the second-line setting. No unexpected safety signals were noted. The rate of fatal pulmonary hemorrhage was consistent with previous bevacizumab trials. The toxicity profile of the bevacizumab-erlotinib combination is favorable compared with either chemotherapy-containing group.
published online ahead of print at www.jco.org on October 1, 2007.
Supported by Genentech Inc, South San Francisco, CA.
Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA; the 18th Annual European Organisation for Research and Treatment of Cancer–National Cancer Institute–American Association for Cancer Research Symposium on Molecular Targets and Cancer Therapeutics, November 7-10, 2006, Prague, Czech Republic; and the 4th Annual International Association for the Study of Lung Cancer International Chicago Symposium on Malignancies of the Chest and Head and Neck, October 26-28, 2006, Chicago, IL.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike Complore Connotea Del.icio.us Digg Facebook Reddit Technorati Twitter What's this?
This article has been cited by other articles:

|
 |

|
 |
 
J. S.W. Lind and E. F. Smit
Review: Angiogenesis inhibitors in the treatment of non-small cell lung cancer
Therapeutic Advances in Medical Oncology,
September 1, 2009;
1(2):
95 - 107.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Horn and A. Sandler
Epidermal Growth Factor Receptor Inhibitors and Antiangiogenic Agents for the Treatment of Non-Small Cell Lung Cancer
Clin. Cancer Res.,
August 15, 2009;
15(16):
5040 - 5048.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. D. Patel, T. A. Hensing, A. Rademaker, E. M. Hart, M. G. Blum, D. T. Milton, and P. D. Bonomi
Phase II Study of Pemetrexed and Carboplatin Plus Bevacizumab With Maintenance Pemetrexed and Bevacizumab As First-Line Therapy for Nonsquamous Non-Small-Cell Lung Cancer
J. Clin. Oncol.,
July 10, 2009;
27(20):
3284 - 3289.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Ichihara, K. Ohashi, N. Takigawa, M. Osawa, A. Ogino, M. Tanimoto, and K. Kiura
Effects of Vandetanib on Lung Adenocarcinoma Cells Harboring Epidermal Growth Factor Receptor T790M Mutation In vivo
Cancer Res.,
June 15, 2009;
69(12):
5091 - 5098.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. S. Miller, J. A. Blessing, C. N. Krasner, R. S. Mannel, P. Hanjani, M. L. Pearl, S. E. Waggoner, and C. H. Boardman
Phase II Evaluation of Pemetrexed in the Treatment of Recurrent or Persistent Platinum-Resistant Ovarian or Primary Peritoneal Carcinoma: A Study of the Gynecologic Oncology Group
J. Clin. Oncol.,
June 1, 2009;
27(16):
2686 - 2691.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. B. Natale, D. Bodkin, R. Govindan, B. G. Sleckman, N. A. Rizvi, A. Capo, P. Germonpre, W. E.E. Eberhardt, P. K. Stockman, S. J. Kennedy, et al.
Vandetanib Versus Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer: Results From a Two-Part, Double-Blind, Randomized Phase II Study
J. Clin. Oncol.,
May 20, 2009;
27(15):
2523 - 2529.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. N. Naumov, M. B. Nilsson, T. Cascone, A. Briggs, O. Straume, L. A. Akslen, E. Lifshits, L. A. Byers, L. Xu, H.-k. Wu, et al.
Combined Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor (EGFR) Blockade Inhibits Tumor Growth in Xenograft Models of EGFR Inhibitor Resistance
Clin. Cancer Res.,
May 15, 2009;
15(10):
3484 - 3494.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Ren, Z. Chu, and L. Mao
Antibodies targeting hepatoma-derived growth factor as a novel strategy in treating lung cancer
Mol. Cancer Ther.,
May 1, 2009;
8(5):
1106 - 1112.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Horn and A. B. Sandler
Angiogenesis in the Treatment of Non-Small Cell Lung Cancer
Proceedings of the ATS,
April 15, 2009;
6(2):
206 - 217.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. A. Pennell and T. J. Lynch Jr.
Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC
Oncologist,
April 1, 2009;
14(4):
399 - 411.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. de Boer, Y. Humblet, J. Wolf, L. Nogova, K. Ruffert, T. Milenkova, R. Smith, A. Godwood, and J. Vansteenkiste
An open-label study of vandetanib with pemetrexed in patients with previously treated non-small-cell lung cancer
Ann. Onc.,
March 1, 2009;
20(3):
486 - 491.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. V. Heymach, L. Paz-Ares, F. De Braud, M. Sebastian, D. J. Stewart, W. E.E. Eberhardt, A. A. Ranade, G. Cohen, J. M. Trigo, A. B. Sandler, et al.
Randomized Phase II Study of Vandetanib Alone or With Paclitaxel and Carboplatin as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer
J. Clin. Oncol.,
November 20, 2008;
26(33):
5407 - 5415.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. R. Nalluri, D. Chu, R. Keresztes, X. Zhu, and S. Wu
Risk of Venous Thromboembolism With the Angiogenesis Inhibitor Bevacizumab in Cancer Patients: A Meta-analysis
JAMA,
November 19, 2008;
300(19):
2277 - 2285.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. S. Herbst and A. Sandler
Bevacizumab and Erlotinib: A Promising New Approach to the Treatment of Advanced NSCLC
Oncologist,
November 1, 2008;
13(11):
1166 - 1176.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. S. Herbst, J. V. Heymach, and S. M. Lippman
Lung Cancer
N. Engl. J. Med.,
September 25, 2008;
359(13):
1367 - 1380.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. L. Estilo, M. Fornier, A. Farooki, D. Carlson, G. Bohle III, and J. M. Huryn
Osteonecrosis of the Jaw Related to Bevacizumab
J. Clin. Oncol.,
August 20, 2008;
26(24):
4037 - 4038.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. M. Thomas, M. J. Ogagan, M. L. Freilino, S. Strychor, D. R. Walsh, W. E. Gooding, J. R. Grandis, and W. C. Zamboni
Antitumor Mechanisms of Systemically Administered Epidermal Growth Factor Receptor Antisense Oligonucleotides in Combination with Docetaxel in Squamous Cell Carcinoma of the Head and Neck
Mol. Pharmacol.,
March 1, 2008;
73(3):
627 - 638.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Bunn Jr., E. B. Haura, and J. V. Heymach
Emerging Therapies for Non-small Cell Lung Cancer
ASCO Educational Book,
January 1, 2008;
2008(1):
e5 - e14.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. E. Stinchcombe and M. A. Socinski
Considerations for Second-Line Therapy of Non-Small Cell Lung Cancer
Oncologist,
January 1, 2008;
13(suppl_1):
28 - 36.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|