Tumor Biology

, Volume 36, Issue 3, pp 1323–1327 | Cite as

Bevacizumab in combination with anticancer drugs for previously treated advanced non-small cell lung cancer

  • Ke-jun Liu
  • Ling-yu Ding
  • Hai-ying Wu


Non-small cell lung cancer (NSCLC) accounts for about 85 % of all lung cancer cases. Patients with NSCLC often have an advanced disease at the time of diagnosis, with a 1-year survival rate about 10–15 % under the best support treatment. As therapeutic methods for lung cancer developed rapidly in recent years, the prognosis of stage IIIB or IV NSCLC also improve to a large extend. Bevacizumab is a monoclonal antibody against VEGFR which inhibits abnormal vascular growth in malignant tumors. In October 2006, bevacizumab was approved by the U.S. Food and Drug Administration (FDA) for first-line use in advanced NSCLC. For patients with advanced NSCLC who failed in previously platinum-based chemotherapy, bevacizumab also showed enhancing efficacy to antitumor drugs recommended by the latest NCCN guideline. This review intends to present the recent progress and prospects of bevacizumab in second- or third-line treatment for patients with refractory NSCLC.


Non-small cell lung cancer (NSCLC) Bevacizumab Platinum-based chemotherapy 



Non-small cell lung cancer


Small cell lung cancer


The U.S. Food and Drug Administration


Eastern Cooperative Oncology Group


Stable disease


Partial remission


Central nervous system


Response Evaluation Criteria in Solid Tumors


Progression-free survival


Overall survival


Epidermal growth factor receptor


Vascular epidermal growth factor receptor


Conflicts of interest



  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Visbal AL, Leighl NB, Feld R, Shepherd FA. Adjuvant chemotherapy for early-stage non-small cell lung cancer. Chest. 2005;128:2933–43.CrossRefPubMedGoogle Scholar
  3. 3.
    Chen F, Cole P, Bina WF. Time trend and geographic patterns of lung adenocarcinoma in the United States, 1973–2002. Cancer Epidemiol Biomarkers Prev. 2007;16:2724–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Laskin JJ, Sandler AB. First-line treatment for advanced non-small-cell lung cancer. Oncology (Williston Park). 2005;19:1671–6. discussion 1678–1680.Google Scholar
  5. 5.
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346:92–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Scagliotti GV, De Marinis F, Rinaldi M, Crino L, Gridelli C, Ricci S, et al. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 2002;20:4285–91.CrossRefPubMedGoogle Scholar
  7. 7.
    Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M. Addition of platinum compounds to a new agent in patients with advanced non-small-cell lung cancer: a literature based meta-analysis of randomised trials. Ann Oncol. 2004;15:1782–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Zatloukal P, Petruzelka L, Zemanova M, Kolek V, Skrickova J, Pesek M, et al. Gemcitabine plus cisplatin vs. Gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer. 2003;41:321–31.CrossRefPubMedGoogle Scholar
  9. 9.
    Stinchcombe TE, Socinski MA. Current treatments for advanced stage non-small cell lung cancer. Proc Am Thorac Soc. 2009;6:233–41.CrossRefPubMedGoogle Scholar
  10. 10.
    Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature. 2005;438:967–74.CrossRefPubMedGoogle Scholar
  12. 12.
    Ferrara N. Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications. Semin Oncol. 2002;29:10–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med. 1971;133:275–88.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3:401–10.CrossRefPubMedGoogle Scholar
  15. 15.
    Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology. 2005;69 Suppl 3:4–10.CrossRefPubMedGoogle Scholar
  16. 16.
    Bremnes RM, Camps C, Sirera R. Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer. 2006;51:143–58.CrossRefPubMedGoogle Scholar
  17. 17.
    Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.CrossRefPubMedGoogle Scholar
  18. 18.
    Jenab-Wolcott J, Giantonio BJ. Bevacizumab: current indications and future development for management of solid tumors. Expert Opin Biol Ther. 2009;9:507–17.CrossRefPubMedGoogle Scholar
  19. 19.
    Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.CrossRefPubMedGoogle Scholar
  20. 20.
    Hainsworth JD, Sosman JA, Spigel DR, Edwards DL, Baughman C, Greco A. Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol. 2005;23:7889–96.CrossRefPubMedGoogle Scholar
  21. 21.
    Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542–50.CrossRefPubMedGoogle Scholar
  22. 22.
    Cohen MH, Gootenberg J, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (avastin) plus carboplatin and paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist. 2007;12:713–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAiL. J Clin Oncol. 2009;27:1227–34.CrossRefPubMedGoogle Scholar
  24. 24.
    Crino L, Dansin E, Garrido P, Griesinger F, Laskin J, Pavlakis N, et al. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (sail, mo19390): a phase 4 study. Lancet Oncol. 2010;11:733–40.CrossRefPubMedGoogle Scholar
  25. 25.
    Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–32.CrossRefPubMedGoogle Scholar
  26. 26.
    Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the tax 326 study group. J Clin Oncol. 2003;21:3016–24.CrossRefPubMedGoogle Scholar
  27. 27.
    Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O’Rourke M, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000;18:2095–103.CrossRefPubMedGoogle Scholar
  28. 28.
    Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22:1589–97.CrossRefPubMedGoogle Scholar
  29. 29.
    Herbst RS, Johnson DH, Mininberg E, Carbone DP, Henderson T, Kim ES, et al. 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. J Clin Oncol. 2005;23:2544–55.CrossRefPubMedGoogle Scholar
  30. 30.
    Herbst RS, O’Neill VJ, Fehrenbacher L, Belani CP, Bonomi PD, Hart L, et al. 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. J Clin Oncol. 2007;25:4743–50.CrossRefPubMedGoogle Scholar
  31. 31.
    Perez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, et al. Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol. 2004;22:3238–47.CrossRefPubMedGoogle Scholar
  32. 32.
    Kris MG, Natale RB, Herbst RS, Lynch Jr TJ, Prager D, Belani CP, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003;290:2149–58.CrossRefPubMedGoogle Scholar
  33. 33.
    Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial-intact 2. J Clin Oncol. 2004;22:785–94.CrossRefPubMedGoogle Scholar
  34. 34.
    Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, De Rosa F, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the tarceva lung cancer investigation trial. J Clin Oncol. 2007;25:1545–52.CrossRefPubMedGoogle Scholar
  35. 35.
    Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, et al. Tribute: a phase III trial of erlotinib hydrochloride (osi-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2005;23:5892–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26:3543–51.CrossRefPubMedGoogle Scholar
  37. 37.
    Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009;374:1432–40.CrossRefPubMedGoogle Scholar
  38. 38.
    Weiss GJ, Zeng C, Kelly K, Tran ZV, Bunn Jr PA. Single-institution experience with pemetrexed and bevacizumab as salvage therapy in advanced non-small-cell lung cancer. Clin Lung Cancer. 2007;8:335–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Adjei AA, Mandrekar SJ, Dy GK, Molina JR, Gandara DR, Ziegler KL, et al. Phase II trial of pemetrexed plus bevacizumab for second-line therapy of patients with advanced non-small-cell lung cancer: NCCTG and SWOG study N0426. J Clin Oncol. 2010;28:614–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Heist RS, Fidias P, Huberman M, Ardman B, Sequist LV, Temel JS, et al. A phase II study of oxaliplatin, pemetrexed, and bevacizumab in previously treated advanced non-small cell lung cancer. J Thorac Oncol. 2008;3:1153–8.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Medical OncologySun Yat-Sen University Cancer CenterGuangzhouChina
  2. 2.State Key Laboratory of Oncology in South ChinaGuangzhouChina
  3. 3.Collaborative Innovation Center of Cancer MedicineGuangzhouChina
  4. 4.Department of Medical OncologyDongguan People’s HospitalDongguanChina

Personalised recommendations