Advertisement

Drugs

, Volume 74, Issue 16, pp 1891–1925 | Cite as

Bevacizumab: A Review of Its Use in Advanced Cancer

  • Gillian M. KeatingEmail author
Adis Drug Evaluation

Abstract

The humanized monoclonal antibody bevacizumab (Avastin®) has been available in the EU since 2005. Results of phase III trials demonstrate that adding intravenous bevacizumab to antineoplastic agents improves progression-free survival and/or overall survival in patients with advanced cancer, including when used as first- or second-line therapy in metastatic colorectal cancer, as first-line therapy in advanced nonsquamous non-small cell lung cancer, as first-line therapy in metastatic renal cell carcinoma, as first-line therapy in metastatic breast cancer, and as first-line therapy in epithelial ovarian, fallopian tube or primary peritoneal cancer or in recurrent, platinum-sensitive or platinum-resistant disease. Results of these studies are supported by the findings of routine oncology practice studies conducted in real-world settings. The tolerability profile of bevacizumab is well defined and adverse events associated with its use (e.g. hypertension, proteinuria, haemorrhage, wound healing complications, arterial thromboembolism, gastrointestinal perforation) are generally manageable. In conclusion, bevacizumab remains an important option for use in patients with advanced cancer.

Keywords

Overall Survival Paclitaxel Bevacizumab Objective Response Rate Pemetrexed 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Disclosure

The preparation of this review was not supported by any external funding. Gillian Keating is a salaried employee of Adis/Springer. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

References

  1. 1.
    Rak JW, St Croix BD, Kerbel RS. Consequences of angiogenesis for tumor progression, metastasis and cancer therapy. Anticancer Drugs. 1995;6(1):3–18.PubMedGoogle Scholar
  2. 2.
    Ferrara N. Vascular endothelial growth factor as a target for anticancer therapy. Oncologist. 2004;9(Suppl 1):2–10.PubMedGoogle Scholar
  3. 3.
    Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25(4):581–611.PubMedGoogle Scholar
  4. 4.
    Ferrara N, Hillan KJ, Gerber H-P, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3(5):391–400.PubMedGoogle Scholar
  5. 5.
    European Medicines Agency. Avastin (bevacizumab): EPAR procedural steps taken before authorisation. 2006. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000582/human_med_000663.jsp&mid=WC0b01ac058001d124. Accessed 17 Sep 2014.
  6. 6.
    European Medicines Agency. Avastin (bevacizumab) 25 mg/mL concentrate for solution for infusion: EU summary of product characteristics. 2014. http://www.ema.europa.eu. Accessed 17 Sep 2014.
  7. 7.
    Jayson GC, de Haas S, Delmar P, et al. Evaluation of plasma VEGFA as potential predictive pan-tumour biomarker for bevacizumab [abstract no. 804]. In: The European Multidisciplinary Cancer Congress; 23–27 Sep 2011; Stockholm.Google Scholar
  8. 8.
    Bais C, Rabe C, Wild N, et al. Comprehensive reassessment of plasma VEGFA (pVEGFA) as a candidate predictive biomarker for bevacizumab (Bv) in 13 pivotal trials (seven indications) [abstract no. 3040]. J Clin Oncol. 2014;32(5 Suppl).Google Scholar
  9. 9.
    Miles D, Faoro L, Wang YV, et al. MERiDiAN: a phase III, randomized, double-blind study of the efficacy, safety, and associated biomarkers of bevacizumab plus paclitaxel compared with paclitaxel plus placebo, as first-line treatment of patients with HER2-negative metastatic breast cancer [abstract no. TPS1142]. J Clin Oncol. 2013;31(15 Suppl).Google Scholar
  10. 10.
    Weickhardt AJ, Williams D, Lee C, et al. Vascular endothelial growth factors (VEGF) and VEGF receptor expression as predictive biomarkers for benefit with bevacizumab in metastatic colorectal cancer (mCRC): analysis of the phase III MAX study [abstract no. 3531]. J Clin Oncol. 2011;29(15 Suppl).Google Scholar
  11. 11.
    Massuti B, Larriba JLG, Lewintre EJ, et al. Study of the correlations between SNPs in angiogenic genes and treatment response/outcome in patients with advanced NSCLC (non-squamous histology) treated in first line with carboplatin, paclitaxel and bevacizumab (CPB): the ANGIOMET study [abstract no. P3.06-035]. J Thorac Oncol. 2013;8(Suppl 2):S1089–90.Google Scholar
  12. 12.
    Muto S, Suzuki H, Higuchi M, et al. Serum nitric oxide could be a predictor for the response of bevacizumab in patients with non-small cell lung cancer [abstract no. P1.06-029]. J Thorac Oncol. 2013;8(Suppl 2):S488.Google Scholar
  13. 13.
    Brennan B, Siu L, Dhesy-Thind B, et al. Pharmacokinetic (PK) interactions between capecitabine (X), oxaliplatin (O) and bevacizumab (A) when used in combination for first-line treatment of metastatic colorectal cancer (MRC) [abstract no. 2554]. J Clin Oncol. 2007;25(18 Suppl).Google Scholar
  14. 14.
    Gerber H-P, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005;65(3):671–80.PubMedGoogle Scholar
  15. 15.
    Presta LG, Chen H, O’Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997;57(20):4593–9.PubMedGoogle Scholar
  16. 16.
    Braghiroli MI, Riechelmann RP, Sabbaga J, et al. Do we need another antiangiogenesis agent for colorectal cancer: are bevacizumab and aflibercept the same? Curr Colorectal Cancer Rep. 2013;9(4):317–25.Google Scholar
  17. 17.
    Lee JJ, Chu E. Sequencing of antiangiogenic agents in the treatment of metastatic colorectal cancer. Clin Colorectal Cancer. 2014;13(3):135–44.PubMedGoogle Scholar
  18. 18.
    Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10(2):145–7.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med. 2001;7(9):987–9.PubMedGoogle Scholar
  20. 20.
    Kerbel RS. Antiangiogenic therapy: a universal chemosensitization strategy for cancer? Science. 2006;312(5777):1171–5.PubMedGoogle Scholar
  21. 21.
    Kolinsky K, Shen B-Q, Zhang Y-E, et al. In vivo activity of novel capecitabine regimens alone and with bevacizumab and oxaliplatin in colorectal cancer xenograft models. Mol Cancer Ther. 2009;8(1):75–82.PubMedGoogle Scholar
  22. 22.
    Kolinsky K, Zhang Y-E, Dugan U, et al. Novel regimens of capecitabine alone and combined with irinotecan and bevacizumab in colorectal cancer xenografts. Anticancer Res. 2009;29(1):91–8.PubMedGoogle Scholar
  23. 23.
    Yanagisawa M, Yorozu K, Kurasawa M, et al. Bevacizumab improves the delivery and efficacy of paclitaxel. Anticancer Drugs. 2010;21(7):687–94.PubMedGoogle Scholar
  24. 24.
    Yanagisawa M, Fujimoto-Ouchi K, Yorozu K, et al. Antitumor activity of bevacizumab in combination with capecitabine and oxaliplatin in human colorectal cancer xenograft models. Oncol Rep. 2009;22(2):241–7.PubMedGoogle Scholar
  25. 25.
    Mabuchi S, Terai Y, Morishige K, et al. Maintenance treatment with bevacizumab prolongs survival in an in vivo ovarian cancer model. Clin Cancer Res. 2008;14(23):7781–9.PubMedGoogle Scholar
  26. 26.
    Oliva P, Decio A, Castiglioni V, et al. Cisplatin plus paclitaxel and maintenance of bevacizumab on tumour progression, dissemination, and survival of ovarian carcinoma xenograft models. Br J Cancer. 2012;107(2):360–9.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Gianni L, Romieu GH, Lichinitser M, et al. AVEREL: a randomized phase III trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013;31(14):1719–25.PubMedGoogle Scholar
  28. 28.
    Miles DW, de Haas SL, Dirix LY, et al. Biomarker results from the AVADO phase 3 trial of first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer. Br J Cancer. 2013;108(5):1052–60.PubMedPubMedCentralGoogle Scholar
  29. 29.
    van Cutsem E, de Haas RJ, Kang Y-K, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol. 2012;30(17):2119–27.PubMedGoogle Scholar
  30. 30.
    Hegde PS, Jubb AM, Chen D, et al. Predictive impact of circulating vascular endothelial growth factor in four phase III trials evaluating bevacizumab. Clin Cancer Res. 2013;19(4):929–37.PubMedGoogle Scholar
  31. 31.
    Smerdel MP, Steffensen KD, Waldstrøm M, et al. The predictive value of serum VEGF in multiresistant ovarian cancer patients treated with bevacizumab. Gynecol Oncol. 2010;118(2):167–71.PubMedGoogle Scholar
  32. 32.
    An S-J, Huang Y-S, Chen Z-H, et al. Posttreatment plasma VEGF levels may be associated with the overall survival of patients with advanced non-small cell lung cancer treated with bevacizumab plus chemotherapy. Med Oncol. 2012;29(2):627–32.PubMedGoogle Scholar
  33. 33.
    Cameron D, Brown J, Dent R, et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol. 2013;14(10):933–42.PubMedGoogle Scholar
  34. 34.
    Abajo A, Rodriguez J, Bitarte N, et al. Dose-finding study and pharmacogenomic analysis of fixed-rate infusion of gemcitabine, irinotecan and bevacizumab in pretreated metastatic colorectal cancer patients. Br J Cancer. 2010;103(10):1529–35.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Schneider BP, Wang M, Radovich M, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008;26(28):4672–8.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Lambrechts D, Claes B, Delmar P, et al. VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. Lancet Oncol. 2012;13(7):724–33.PubMedGoogle Scholar
  37. 37.
    Formica V, Palmirotta R, Del Monte G, et al. Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab. Int J Colorectal Dis. 2011;26(2):143–51.PubMedGoogle Scholar
  38. 38.
    Etienne-Grimaldi M-C, Formento P, Degeorges A, et al. Prospective analysis of the impact of VEGF-A gene polymorphisms on the pharmacodynamics of bevacizumab-based therapy in metastatic breast cancer patients. Br J Clin Pharmacol. 2011;71(6):921–8.PubMedPubMedCentralGoogle Scholar
  39. 39.
    de Haas S, Delmar P, Bansal AT, et al. Genetic variability of VEGF pathway genes in six randomized phase III trials assessing the addition of bevacizumab to standard therapy. Angiogenesis. 2014. doi: 10.1007/s10456-014-9438-1.PubMedGoogle Scholar
  40. 40.
    Sohn BS, Park SJ, Kim JE, et al. Single-nucleotide polymorphisms in the vascular endothelial growth factor pathway and outcomes of patients treated with first-line cytotoxic chemotherapy combined with bevacizumab for advanced colorectal cancer. Oncology. 2014;87(5):280–92.PubMedGoogle Scholar
  41. 41.
    Malka D, Boige V, Jacques N, et al. Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab. Ann Oncol. 2012;23(4):919–27.PubMedGoogle Scholar
  42. 42.
    Manzoni M, Mariucci S, Delfanti S, et al. Circulating endothelial cells and their apoptotic fraction are mutually independent predictive biomarkers in bevacizumab-based treatment for advanced colorectal cancer. J Cancer Res Clin Oncol. 2012;138(7):1187–96.PubMedGoogle Scholar
  43. 43.
    Narita Y, Taniguchi H, Komori A, et al. CA19-9 level as a prognostic and predictive factor of bevacizumab efficacy in metastatic colorectal cancer patients undergoing oxaliplatin-based chemotherapy. Cancer Chemother Pharmacol. 2014;73(2):409–16.PubMedGoogle Scholar
  44. 44.
    Zhao Y-Y, Xue C, Jiang W, et al. Predictive value of intratumoral microvascular density in patients with advanced non-small cell lung cancer receiving chemotherapy plus bevacizumab. J Thorac Oncol. 2012;7(1):71–5.PubMedGoogle Scholar
  45. 45.
    Schneider BP, Gray RJ, Radovich M, et al. Prognostic and predictive value of tumor vascular endothelial growth factor gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial. Clin Cancer Res. 2013;19(5):1281–9.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Slaughter KN, Thai T, Penaroza S, et al. Measurements of adiposity as clinical biomarkers for first-line bevacizumab-based chemotherapy in epithelial ovarian cancer. Gynecol Oncol. 2014;133(1):11–5.PubMedGoogle Scholar
  47. 47.
    Collinson F, Hutchinson M, Craven RA, et al. Predicting response to bevacizumab in ovarian cancer: a panel of potential biomarkers informing treatment selection. Clin Cancer Res. 2013;19(18):5227–39.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001;19(3):843–50.PubMedGoogle Scholar
  49. 49.
    Lu J-F, Bruno R, Eppler S, et al. Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother Pharmacol. 2008;62(5):779–86.PubMedGoogle Scholar
  50. 50.
    Li J, Gupta M, Jin D, et al. Characterization of the long-term pharmacokinetics of bevacizumab following last dose in patients with resected stage II and III carcinoma of the colon. Cancer Chemother Pharmacol. 2013;71(3):575–80.PubMedGoogle Scholar
  51. 51.
    Wu J-Y, Wu X-N, Ding L, et al. Phase I safety and pharmacokinetic study of bevacizumab in Chinese patients with advanced cancer. Chin Med J. 2010;123(7):901–6.PubMedGoogle Scholar
  52. 52.
    Zhi J, Chen E, Major P, et al. A multicenter, randomized, open-label study to assess the steady-state pharmacokinetics of bevacizumab given with either XELOX or FOLFOX-4 in patients with metastatic colorectal cancer. Cancer Chemother Pharmacol. 2011;68(5):1199–206.PubMedGoogle Scholar
  53. 53.
    Horita Y, Yamada Y, Hirashima Y, et al. Effects of bevacizumab on plasma concentration of irinotecan and its metabolites in advanced colorectal cancer patients receiving FOLFIRI with bevacizumab as second-line chemotherapy. Cancer Chemother Pharmacol. 2010;65(3):467–71.PubMedGoogle Scholar
  54. 54.
    Farkouh A, Scheithauer W, Buchner P, et al. Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab. Anticancer Res. 2014;34(7):3669–73.PubMedGoogle Scholar
  55. 55.
    Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42.PubMedGoogle Scholar
  56. 56.
    Saltz LB, Clarke S, Díaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26(12):2013–9.PubMedGoogle Scholar
  57. 57.
    Guan Z-Z, Xu J-M, Luo R-C, et al. Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial. Chin J Cancer. 2011;30(10):682–9.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Passardi A, Scarpi E, Cavanna L, et al. Effectiveness of bevacizumab added to gold standard chemotherapy in metastatic colorectal cancer (mCRC): final results from the ITACA randomized clinical trial [abstract no. 3517]. J Clin Oncol. 2013;31(15 Suppl).Google Scholar
  59. 59.
    Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14(11):1077–85.PubMedGoogle Scholar
  60. 60.
    Fuchs CS, Marshall J, Mitchell E, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007;25(30):4779–86.PubMedGoogle Scholar
  61. 61.
    Falcone A, Cremolini C, Masi G, et al. FOLFOXIRI/bevacizumab (bev) versus FOLFIRI/bev as first-line treatment in unresectable metastatic colorectal cancer (mCRC) patients (pts): results of the phase III TRIBE trial by GONO group [abstract no. 3505]. J Clin Oncol. 2013;31(15 Suppl).Google Scholar
  62. 62.
    Yamazaki K, Nagase M, Tamagawa H, et al. A randomized phase III trial of mFOLFOX6 plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment for metastatic colorectal cancer: West Japan Oncology Group study 4407G (WJOG4407G) [abstract no. 3534]. In: 2014 ASCO Annual Meeting; 30 May-3 Jun 2014; Chicago (IL).Google Scholar
  63. 63.
    Yamada Y, Takahari D, Matsumoto H, et al. Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2013;14(13):1278–86.PubMedGoogle Scholar
  64. 64.
    Pectasides D, Papaxoinis G, Kalogeras KT, et al. XELIRI-bevacizumab versus FOLFIRI-bevacizumab as first-line treatment in patients with metastatic colorectal cancer: a Hellenic Cooperative Oncology Group phase III trial with collateral biomarker analysis. BMC Cancer. 2012;12:271.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Venook AP, Niedzwiecki D, Lenzm H-J, et al. CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC) [abstract no. LBA3]. In: 2014 ASCO Annual Meeting; 30 May–3 Jun 2014; Chicago (IL).Google Scholar
  66. 66.
    Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065–75.PubMedGoogle Scholar
  67. 67.
    Loupakis F, Cremolini C, Masi G, et al. FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (MCRC): results of the phase III randomized TRIBE trial [abstract no. 336]. J Clin Oncol. 2013;31(4 Suppl).Google Scholar
  68. 68.
    Nakamura M, Yamada Y, Takahari D, et al. Updated results of the SOFT study: a randomized phase III trial of S-1/oxaliplatin (SOX) plus bevacizumab versus 5-FU/l-LV/oxaliplatin (mFOLFOX6) plus bevacizumab in patients with metastatic colorectal cancer (mCRC) [abstract no. 3586]. In: 2014 ASCO Annual Meeting; 30 May–3 Jun 2014; Chicago (IL).Google Scholar
  69. 69.
    Loupakis F, Cremolini C, Lonardi S, et al. Subgroup analysis in RAS mutant, BRAF mutant and all-wt mCRC pts treated with FOLFOXIRI plus bevacizumab (bev) or FOLFIRI plus bev in the TRIBE study [abstract no. 3519]. In: 2014 ASCO Annual Meeting; 30 May–3 Jun 2014; Chicago (IL).Google Scholar
  70. 70.
    Cassidy J, Clarke S, Díaz-Rubio E, et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008;26(12):2006–12.PubMedGoogle Scholar
  71. 71.
    Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;25(12):1539–44.PubMedGoogle Scholar
  72. 72.
    Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14(1):29–37.PubMedGoogle Scholar
  73. 73.
    Masi G, Loupakis F, Salvatore L, et al. Second-line chemotherapy (CT) with or without bevacizumab (BV) in metastatic colorectal cancer (mCRC) patients (pts) who progressed to a first-line treatment containing BV: updated results of the phase III ‘BEBYP’ trial by the Gruppo Oncologico Nord Ovest (GONO) [abstract no. 3615]. J Clin Oncol. 2013;31(15 Suppl).Google Scholar
  74. 74.
    Bendell JC, Bekaii-Saab TS, Cohn AL, et al. Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOX-bevacizumab or FOLFIRI-bevacizumab: results from ARIES, a bevacizumab observational cohort study. Oncologist. 2012;17(12):1486–95.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Kozloff M, Yood MU, Berlin J, et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist. 2009;14(9):862–70.PubMedGoogle Scholar
  76. 76.
    Van Cutsem E, Rivera F, Berry S, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. 2009;20(11):1842–7.PubMedGoogle Scholar
  77. 77.
    Kiss I, Bortlicek Z, Melichar B, et al. Efficacy and toxicity of bevacizumab on combination with chemotherapy in different lines of treatment for metastatic colorectal carcinoma. Anticancer Res. 2014;34(2):949–54.PubMedGoogle Scholar
  78. 78.
    Meyerhardt JA, Li L, Sanoff HK, et al. Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer. J Clin Oncol. 2012;30(6):608–15.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Grothey A, Flick ED, Cohn AL, et al. Bevacizumab exposure beyond first disease progression in patients with metastatic colorectal cancer: analyses of the ARIES observational cohort study. Pharmacoepidemiol Drug Saf. 2014;23(7):726–34.PubMedGoogle Scholar
  80. 80.
    Grothey A, Sugrue MM, Purdie DM, et al. Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol. 2008;26(33):5326–34.PubMedGoogle Scholar
  81. 81.
    Buchler T, Pavlik T, Melichar B, et al. Bevacizumab with 5-fluorouracil, leucovorin, and oxaliplatin versus bevacizumab with capecitabine and oxaliplatin for metastatic colorectal carcinoma: results of a large registry-based cohort analysis. BMC Cancer. 2014;14(1):323.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Slavicek L, Pavlik T, Tomasek J, et al. Efficacy and safety of bevacizumab in elderly patients with metastatic colorectal cancer: results from the Czech population-based registry. BMC Gastroenterol. 2014;14:53.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Zhou C, Chen G, Liu X, et al. BEYOND: a randomized, double-blind, placebo-controlled, multicentre, phase III study of first-line carboplatin/paclitaxel (CP) plus bevacizumab (BV) or placebo (PL) in Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) [abstract no. MO06.13]. J Thorac Oncol. 2013;8(Suppl 2):S293.Google Scholar
  84. 84.
    Reck M, von Pawel J, Zatloukal P, 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(8):1227–34.PubMedGoogle Scholar
  85. 85.
    Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542–50.PubMedGoogle Scholar
  86. 86.
    Patel JD, Socinski MA, Garon EB, et al. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013;31(34):4349–57.PubMedPubMedCentralGoogle Scholar
  87. 87.
    Schuette W, Nagel S, Schneider C-P, et al. 65 plus: a randomized phase III trial of pemetrexed and bevacizumab versus pemetrexed, bevacizumab, and carboplatin as first-line treatment for elderly patients with advanced nonsquamous, non-small cell lung cancer (NSCLC) [abstract no. 8013]. J Clin Oncol. 2013;31(15 Suppl).Google Scholar
  88. 88.
    Zinner R, Ross HJ, Weaver R, et al. Randomized, open-label, phase III study of pemetrexed plus carboplatin (PemC) followed by maintenance pemetrexed versus paclitaxel/carboplatin/bevacizumab (PCB) followed by maintenance bevacizumab in patients with advanced nonsquamous (NS) non-small cell lung cancer (NSCLC) [abstract no. LBA8003]. J Clin Oncol. 2013;31(15 Suppl).Google Scholar
  89. 89.
    Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004;22(11):2184–91.PubMedGoogle Scholar
  90. 90.
    Peters S, Adjei AA, Gridelli C, et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):756–64.Google Scholar
  91. 91.
    Brahmer JR, Dahlberg SE, Gray RJ, et al. Sex differences in outcome with bevacizumab therapy: analysis of patients with advanced-stage non-small cell lung cancer treated with or without bevacizumab in combination with paclitaxel and carboplatin in the Eastern Cooperative Oncology Group Trial 4599. J Thorac Oncol. 2011;6(1):103–8.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Ramalingam SS, Dahlberg SE, Langer CJ, et al. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008;26(1):60–5.PubMedGoogle Scholar
  93. 93.
    Reck M, von Pawel J, Zatloukal P, et al. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol. 2010;21(9):1804–9.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Crinò L, Dansin E, Garrido P, 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(8):733–40.PubMedGoogle Scholar
  95. 95.
    Lynch TJ Jr, Spigel DR, Brahmer J, et al. Safety and effectiveness of bevacizumab-containing treatment for non-small-cell lung cancer: final results of the ARIES observational cohort study. J Thorac Oncol. 2014;9(9):1332–9.PubMedGoogle Scholar
  96. 96.
    Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370(9605):2103–11.PubMedGoogle Scholar
  97. 97.
    Rini BI, Halabi S, Rosenberg JE, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008;26(33):5422–8.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Melichar B, Bracarda S, Matveev V, et al. A multinational phase II trial of bevacizumab with low-dose interferon-α2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN. Ann Oncol. 2013;24(9):2396–402.PubMedGoogle Scholar
  99. 99.
    Escudier B, Bellmunt J, Négrier S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010;28(13):2144–50.PubMedGoogle Scholar
  100. 100.
    Rini BI, Halabi S, Rosenberg JE, et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010;28(13):2137–43.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Melichar B, Koralewski P, Ravaud A, et al. First-line bevacizumab combined with reduced dose interferon-α2a is active in patients with metastatic renal cell carcinoma. Ann Oncol. 2008;19(8):1470–6.PubMedGoogle Scholar
  102. 102.
    Robert NJ, Dieras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011;29(10):1252–60.PubMedGoogle Scholar
  103. 103.
    Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357(26):2666–76.PubMedGoogle Scholar
  104. 104.
    Lang I, Brodowicz T, Ryvo L, et al. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lancet Oncol. 2013;14(2):125–33.PubMedGoogle Scholar
  105. 105.
    Rochiltz C, von Moos R, Bigler M, et al. SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel versus bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer: a multicenter, randomized phase III trial [abstract no. 518]. In: 2014 ASCO Annual Meeting; 30 May–3 Jun 2014; Chicago (IL).Google Scholar
  106. 106.
    European Medicines Agency. Assessment report for Avastin (bevacizumab): procedure No. EMEA/H/C/582/A-20/038. 2011. http://www.ema.europa.eu. Accessed 17 Sep 2014.
  107. 107.
    Gray R, Bhattacharya S, Bowden C, et al. Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2009;27(30):4966–72.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Cella D, Wang M, Wagner L, et al. Survival-adjusted health-related quality of life (HRQL) among patients with metastatic breast cancer receiving paclitaxel plus bevacizumab versus paclitaxel alone: results from Eastern Cooperative Oncology Group Study 2100 (E2100). Breast Cancer Res Treat. 2011;130(3):855–61.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Inbar MJ, Lang I, Kahan Z, et al. Efficacy of first-line bevacizumab (BEV)-based therapy for metastatic triple-negative breast cancer (TNBC): subgroup analysis of TURANDOT [abstract no. 1040]. J Clin Oncol. 2013;31(15 Suppl).Google Scholar
  110. 110.
    Schneeweiss A, Fett W, Aktas B, et al. AVANTI: a non-interventional study examining the combination of bevacizumab with paclitaxel or capecitabine in metastatic breast cancer [abstract no. P4-14-04]. In: 36th Annual San Antonio Breast Cancer Symposium; 10–14 Dec 2013; San Antonio (TX).Google Scholar
  111. 111.
    Dank M, Budi L, Piko B, et al. First-line bevacizumab-paclitaxel in 220 patients with metastatic breast cancer: results from the AVAREG study. Anticancer Res. 2014;34(3):1275–80.PubMedGoogle Scholar
  112. 112.
    Smith I, Pierga J-Y, Biganzoli L, et al. Final overall survival results and effect of prolonged (≥1 year) first-line bevacizumab-containing therapy for metastatic breast cancer in the ATHENA trial. Breast Cancer Res Treat. 2011;130(1):133–43.PubMedGoogle Scholar
  113. 113.
    Llombart-Cussac A, Pivot X, Biganzoli L, et al. A prognostic factor index for overall survival in patients receiving first-line chemotherapy for HER2-negative advanced breast cancer: an analysis of the ATHENA trial. Breast. 2014. doi: 10.1016/j.breast.2014.06.017.PubMedGoogle Scholar
  114. 114.
    Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473–83.PubMedGoogle Scholar
  115. 115.
    Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.PubMedGoogle Scholar
  116. 116.
    Burger RA, Brady MF, Rhee J, et al. Independent radiologic review of the Gynecologic Oncology Group Study 0218, a phase III trial of bevacizumab in the primary treatment of advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. Gynecol Oncol. 2013;131(1):21–6.PubMedPubMedCentralGoogle Scholar
  117. 117.
    Randall L, Burger R, Nguyen H, et al. Outcome differences in patients with advanced epithelial ovarian, primary peritoneal and fallopian tube cancers treated with and without bevacizumab [abstract no. 80]. Gynecol Oncol. 2013;130(1):e33–4.Google Scholar
  118. 118.
    Monk BJ, Huang HQ, Burger RA, et al. Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2013;128(3):573–8.PubMedGoogle Scholar
  119. 119.
    Oza AM, Perren TJ, Swart AM, et al. ICON7: final overall survival results in the GCIG phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer [abstract plus slide presentation]. In: European Cancer Congress 2013; 27 Sep–1 Oct 2013; Amsterdam.Google Scholar
  120. 120.
    Stark D, Nankivell M, Pujade-Lauraine E, et al. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol. 2013;14(3):236–43.PubMedPubMedCentralGoogle Scholar
  121. 121.
    Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012;30(17):2039–45.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Aghajanian C, Goff B, Nycum LR, et al. Independent radiologic review: bevacizumab in combination with gemcitabine and carboplatin in recurrent ovarian cancer. Gynecol Oncol. 2014;133(1):105–10.PubMedGoogle Scholar
  123. 123.
    Aghajanian C, Nycum LR, Goff B, et al. Updated overall survival analysis in OCEANS, a randomized phase 3 trial of gemcitabine (G) + carboplatin (C) and bevacizumab (BV) or placebo (PL) followed by BV or PL in platinum-sensitive recurrent epithelial ovarian (ROC), primary peritoneal (PPC) or fallopian tube cancer [abstract no. 967O]. Ann Oncol. 2012;23(Suppl 9):9319.Google Scholar
  124. 124.
    Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32(13):1302–8.PubMedGoogle Scholar
  125. 125.
    Husain A, Wang YV, Frederiksen R, et al. Independent radiologic review of AURELIA, a phase 3 trial of bevacizumab (BV) plus chemotherapy (CT) for platinum-resistant recurrent ovarian cancer (OC) [abstract no. 5540]. In: 2014 ASCO Annual Meeting; 30 May–3 Jun 2014; Chicago (IL).Google Scholar
  126. 126.
    Stockler MR, Hilpert F, Friedlander M, et al. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014;32(13):1309–16.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Randall LM, Monk BJ. Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol. 2010;117(3):497–504.PubMedPubMedCentralGoogle Scholar
  128. 128.
    Saif MW. Managing bevacizumab-related toxicities in patients with colorectal cancer. J Support Oncol. 2009;7(6):245–51.PubMedGoogle Scholar
  129. 129.
    Syrigos KN, Karapanagiotou E, Boura P, et al. Bevacizumab-induced hypertension: pathogenesis and management. BioDrugs. 2011;25(3):159–69.PubMedGoogle Scholar
  130. 130.
    An MM, Zou Z, Shen H, et al. Incidence and risk of significantly raised blood pressure in cancer patients treated with bevacizumab: an updated meta-analysis. Eur J Clin Pharmacol. 2010;66(8):813–21.PubMedGoogle Scholar
  131. 131.
    Scartozzi M, Galizia E, Chiorrini S, et al. Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol. 2009;20(2):227–30.PubMedGoogle Scholar
  132. 132.
    Gampenrieder SP, Romeder F, Muß C, et al. Hypertension as a predictive marker for bevacizumab in metastatic breast cancer: results from a retrospective matched-pair analysis. Anticancer Res. 2014;34(1):227–33.PubMedGoogle Scholar
  133. 133.
    Dahlberg SE, Sandler AB, Brahmer JR, et al. Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599. J Clin Oncol. 2010;28(6):949–54.PubMedPubMedCentralGoogle Scholar
  134. 134.
    Österlund P, Soveri L-M, Isoniemi H, et al. Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy. Br J Cancer. 2011;104(4):599–604.PubMedPubMedCentralGoogle Scholar
  135. 135.
    De Stefano A, Carlomagno C, Pepe S, et al. Bevacizumab-related arterial hypertension as a predictive marker in metastatic colorectal cancer patients. Cancer Chemother Pharmacol. 2011;68(5):1207–13.PubMedGoogle Scholar
  136. 136.
    Bono P, Elfving H, Utriainen T, et al. Hypertension and clinical benefit of bevacizumab in the treatment of advanced renal cell carcinoma. Ann Oncol. 2009;20(2):393–4.PubMedGoogle Scholar
  137. 137.
    Pant S, Martin LK, Geyer S, et al. Treatment-related hypertension as a pharmacodynamic biomarker for the efficacy of bevacizumab in advanced pancreas cancer: a pooled analysis of 4 prospective trials of gemcitabine-based therapy with bevacizumab. Am J Clin Oncol. 2014. doi: 10.1097/COC.0000000000000108.PubMedPubMedCentralGoogle Scholar
  138. 138.
    Hurwitz HI, Douglas PS, Middleton JP, et al. Analysis of early hypertension and clinical outcome with bevacizumab: results from seven phase III studies. Oncologist. 2013;18(3):273–80.PubMedPubMedCentralGoogle Scholar
  139. 139.
    Miles DW, Chan A, Dirix LY, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010;28(20):3239–47.PubMedGoogle Scholar
  140. 140.
    Van Cutsem E, Vervenne WL, Bennouna J, et al. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol. 2009;27(13):2231–7.PubMedGoogle Scholar
  141. 141.
    Miller K, O’Neill AM, Dang CT, et al. Bevacizumab (Bv) in the adjuvant treatment of HER2-negative breast cancer: final results from Eastern Cooperative Oncology Group E5103 [abstract no. 500]. In: 2014 ASCO Annual Meeting; 30 May–3 Jun 2014; Chicago (IL).Google Scholar
  142. 142.
    Schneider BP, Li L, Shen F, et al. Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100. Br J Cancer. 2014;111(6):1241–8.PubMedPubMedCentralGoogle Scholar
  143. 143.
    Yeh J, Frieze D, Martins R, et al. Clinical utility of routine proteinuria evaluation in treatment decisions of patients receiving bevacizumab for metastatic solid tumors. Ann Pharmacother. 2010;44(6):1010–5.PubMedGoogle Scholar
  144. 144.
    Lafayette RA, McCall B, Li N, et al. Incidence and relevance of proteinuria in bevacizumab-treated patients: pooled analysis from randomized controlled trials. Am J Nephrol. 2014;40(1):75–83.PubMedGoogle Scholar
  145. 145.
    Smith IE, Pierga JY, Biganzoli L, et al. First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: safety and efficacy in an open-label study in 2,251 patients. Ann Oncol. 2011;22(3):595–602.PubMedGoogle Scholar
  146. 146.
    Cortés J, Caralt M, Delaloge S, et al. Safety of bevacizumab in metastatic breast cancer patients undergoing surgery. Eur J Cancer. 2012;48(4):475–81.PubMedGoogle Scholar
  147. 147.
    Hang XF, Xu WS, Wang JX, et al. Risk of high-grade bleeding in patients with cancer treated with bevacizumab: a meta-analysis of randomized controlled trials. Eur J Clin Pharmacol. 2011;67(6):613–23.PubMedGoogle Scholar
  148. 148.
    Besse B, Lasserre SF, Compton P, et al. Bevacizumab safety in patients with central nervous system metastases. Clin Cancer Res. 2010;16(1):269–78.PubMedGoogle Scholar
  149. 149.
    Hapani S, Chu D, Wu S. Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol. 2009;10(6):559–68.PubMedGoogle Scholar
  150. 150.
    Stone RL, Sood AK, Coleman RL. Collateral damage: toxic effects of targeted antiangiogenic therapies in ovarian cancer. Lancet Oncol. 2010;11(5):465–75.PubMedPubMedCentralGoogle Scholar
  151. 151.
    Kabbinavar FF, Flynn PJ, Kozloff M, et al. Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer: results from a large treatment observational cohort study. Eur J Cancer. 2012;48(8):1126–32.PubMedGoogle Scholar
  152. 152.
    Chau I, Cunningham D. Bevacizumab-associated gastrointestinal perforation. Lancet Oncol. 2009;10(6):534–6.PubMedGoogle Scholar
  153. 153.
    Abu-Hejleh T, Mezhir JJ, Goodheart MJ, et al. Incidence and management of gastrointestinal perforation from bevacizumab in advanced cancers. Curr Oncol Rep. 2012;14(4):277–84.PubMedGoogle Scholar
  154. 154.
    Scappaticci FA, Skillings JR, Holden SN, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst. 2007;99(16):1232–9.PubMedGoogle Scholar
  155. 155.
    Cassidy J, Saltz LB, Giantonio BJ, et al. Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol. 2010;136(5):737–43.PubMedGoogle Scholar
  156. 156.
    Choueiri TK, Mayer EL, Je Y, et al. Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol. 2011;29(6):632–8.PubMedGoogle Scholar
  157. 157.
    Cobleigh MA, Langmuir VK, Sledge GW, et al. A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol. 2003;30(5 Suppl 16):117–24.PubMedGoogle Scholar
  158. 158.
    Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005;23(4):792–9.PubMedGoogle Scholar
  159. 159.
    Verma N, Swain SM. Bevacizumab and heart failure risk in patients with breast cancer: a thorn in the side? J Clin Oncol. 2011;29(6):603–6.PubMedGoogle Scholar
  160. 160.
    Reck M, Barlesi F, Crinò L, et al. Predicting and managing the risk of pulmonary haemorrhage in patients with NSCLC treated with bevacizumab: a consensus report from a panel of experts. Ann Oncol. 2012;23(5):1111–20.PubMedGoogle Scholar
  161. 161.
    Socinski MA, Langer CJ, Huang JE, et al. Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases [in French]. J Clin Oncol. 2009;27(31):5255–61.PubMedGoogle Scholar
  162. 162.
    Kuse N, Yoshimori K, Ueyama M, et al. Safety of bevacizumab-containing chemotherapy in non-small-cell lung cancer patients with brain metastases. Ann Cancer Res Ther. 2012;20(2):47–51.Google Scholar
  163. 163.
    Lang I, Inbar MJ, Kahán Z, et al. Safety results from a phase III study (TURANDOT trial by CECOG) of first-line bevacizumab in combination with capecitabine or paclitaxel for HER-2-negative locally recurrent or metastatic breast cancer. Eur J Cancer. 2012;48(17):3140–9.PubMedGoogle Scholar
  164. 164.
    Burger RA, Brady MF, Bookman MA, et al. Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2014;32(12):1210–7.PubMedPubMedCentralGoogle Scholar
  165. 165.
    Colombo N, Selle F, Korach J, et al. Assessment of safety of surgery in patients with ovarian cancer treated with carboplatin/paclitaxel/bevacizumab in the ROSiA routine oncology practice study [abstract]. Int J Gynecol Cancer. 2013;23(8 Suppl 1):128–9.Google Scholar
  166. 166.
    Cannistra SA, Matulonis UA, Penson RT, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007;25(33):5180–6.PubMedGoogle Scholar
  167. 167.
    Richardson DL, Backes FJ, Hurt JD, et al. Which factors predict bowel complications in patients with recurrent epithelial ovarian cancer being treated with bevacizumab? Gynecol Oncol. 2010;118(1):47–51.PubMedGoogle Scholar
  168. 168.
    Tanyi JL, McCann G, Hagemann AR, et al. Clinical predictors of bevacizumab-associated gastrointestinal perforation. Gynecol Oncol. 2011;120(3):464–9.PubMedGoogle Scholar
  169. 169.
    Hayes DF. Bevacizumab treatment for solid tumors: boon or bust? JAMA. 2011;305(5):506–8.PubMedGoogle Scholar
  170. 170.
    Tappenden P, Jones R, Paisley S, et al. The cost-effectiveness of bevacizumab in the first-line treatment of metastatic colorectal cancer in England and Wales. Eur J Cancer. 2007;43(17):2487–94.PubMedGoogle Scholar
  171. 171.
    Carter HE, Zannino D, John Simes R, et al. The cost effectiveness of bevacizumab when added to capecitabine, with or without mitomycin-C, in first line treatment of metastatic colorectal cancer: results from the Australasian phase III MAX study. Eur J Cancer. 2014;50(3):535–43.PubMedGoogle Scholar
  172. 172.
    Barnett JC, AlvarezSecord A, Cohn DE, et al. Cost effectiveness of alternative strategies for incorporating bevacizumab into the primary treatment of ovarian cancer. Cancer. 2013;119(20):3653–61.PubMedGoogle Scholar
  173. 173.
    Cohn DE, Kim KH, Resnick KE, et al. At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer? A cost-effectiveness analysis. J Clin Oncol. 2011;29(10):1247–51.PubMedGoogle Scholar
  174. 174.
    Bevacizumab in combination with paclitaxel and carboplatin for the first-line treatment of ovarian cancer: NICE technology appraisals (TA284). 2013. http://www.nice.org.uk/Guidance/TA284. Accessed 17 Sep 2014.
  175. 175.
    Mehta DA, Hay JW. Cost-effectiveness of adding bevacizumab to first line therapy for patients with advanced ovarian cancer. Gynecol Oncol. 2014;132(3):677–83.PubMedGoogle Scholar
  176. 176.
    Chan JK, Herzog TJ, Hu L, et al. Bevacizumab in treatment of high-risk ovarian cancer: a cost-effectiveness analysis. Oncologist. 2014;19(5):523–7.PubMedPubMedCentralGoogle Scholar
  177. 177.
    Montero AJ, Avancha K, Glück S, et al. A cost-benefit analysis of bevacizumab in combination with paclitaxel in the first-line treatment of patients with metastatic breast cancer. Breast Cancer Res Treat. 2012;132(2):747–51.PubMedGoogle Scholar
  178. 178.
    Dedes KJ, Matter-Walstra K, Schwenkglenks M, et al. Bevacizumab in combination with paclitaxel for HER-2 negative metastatic breast cancer: an economic evaluation. Eur J Cancer. 2009;45(8):1397–406.PubMedGoogle Scholar
  179. 179.
    Lambrechts D, Lenz H-J, de Haas S, et al. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol. 2013;31(9):1219–30.PubMedGoogle Scholar
  180. 180.
    Maru D, Venook AP, Ellis LM. Predictive biomarkers for bevacizumab: are we there yet? Clin Cancer Res. 2013;19(11):2824–7.PubMedGoogle Scholar
  181. 181.
    Chong G, Tebbutt NC. Using bevacizumab with different chemotherapeutic regimens in metastatic colorectal cancer: balancing utility with low toxicity. Ther Adv Med Oncol. 2010;2(5):309–17.PubMedPubMedCentralGoogle Scholar
  182. 182.
    Ebos JM, Lee CR, Cruz-Munoz W, et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009;15(3):232–9.PubMedPubMedCentralGoogle Scholar
  183. 183.
    Pàez-Ribes M, Allen E, Hudock J, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009;15(3):220–31.PubMedPubMedCentralGoogle Scholar
  184. 184.
    Mancuso MR, Davis R, Norberg SM, et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest. 2006;116(10):2610–21.PubMedPubMedCentralGoogle Scholar
  185. 185.
    Conley SJ, Gheordunescu E, Kakarala P, et al. Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia. Proc Natl Acad Sci USA. 2012;109(8):2784–9.PubMedGoogle Scholar
  186. 186.
    Miles D, Harbeck N, Escudier B, et al. Disease course patterns after discontinuation of bevacizumab: pooled analysis of randomized phase III trials. J Clin Oncol. 2011;29(1):83–8.PubMedGoogle Scholar
  187. 187.
    Allegra CJ, Yothers G, O’Connell MJ, et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol. 2011;29(1):11–6.PubMedGoogle Scholar
  188. 188.
    Van Cutsem E, Nordlinger B, Cervantes A. Advanced colorectal cancer: ESMO clinical practice guidelines for treatment. Ann Oncol. 2010;21(Suppl 5):v93–7.PubMedGoogle Scholar
  189. 189.
    National Comprehensive Cancer Network. NCCN clinical practice guidlines in oncology (NCCN guidelines). Colon cancer: version 1.2015. 2014. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 17 Sep 2014.
  190. 190.
    National Comprehensive Cancer Network. NCCN clinical practice guidlines in oncology (NCCN guidelines). Rectal cancer: version 1.2015. 2014. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 17 Sep 2014.
  191. 191.
    Simkens LHJ, Koopman M, Punt CJA. Optimal duration of systemic treatment in metastatic colorectal cancer. Curr Opin Oncol. 2014;26(4):448–53.PubMedGoogle Scholar
  192. 192.
    Di Bartolomeo M, Pietrantonio F, Martinetti A, et al. Role of the antiangiogenic agent bevacizumab in the treatment of elderly patients with metastatic colorectal cancer. Drugs Aging. 2011;28:83–91.PubMedGoogle Scholar
  193. 193.
    Koopman M, Simkens L, May AM, et al. Final results and subgroup analyses of the phase 3 CAIRO3 study: maintenance treatment with capecitabine + bevacizumab versus observation after induction treatment with chemotherapy + bevacizumab in metastatic colorectal cancer (mCRC) [abstract no. 3504]. In: 2014 ASCO Annual Meeting; 30 May–3 Jun 2014; Chicago (IL).Google Scholar
  194. 194.
    Koeberle D, Betticher D, von Moos R, et al. Bevacizumab continuation versus no continuation after first-line chemo-bevacizumab therapy in patients with metastatic colorectal cancer: a randomized phase 3 non-inferiority trial (SAKK 41/06) [abstract no. V387]. Onkologie. 2013;36(Suppl 7):104.Google Scholar
  195. 195.
    Díaz-Rubio E, Gómez-España A, Massutí B, et al. First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. Oncologist. 2012;17(1):15–25.PubMedPubMedCentralGoogle Scholar
  196. 196.
    Vokes EE, Salgia R, Karrison TG. Evidence-based role of bevacizumab in non-small cell lung cancer. Ann Oncol. 2013;24(1):6–9.PubMedGoogle Scholar
  197. 197.
    Lauro S, Onesti CE, Righini R, et al. The use of bevacizumab in non-small cell lung cancer: an update. Anticancer Res. 2014;34(4):1537–45.PubMedGoogle Scholar
  198. 198.
    National Comprehensive Cancer Network. NCCN clinical practice guidlines in oncology (NCCN guidelines). Non-small cell lung cancer: version 4.2014. 2014. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 17 Sep 2014.
  199. 199.
    Barlesi F, Scherpereel A, Rittmeyer A, et al. Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089). J Clin Oncol. 2013;31(24):3004–11.PubMedGoogle Scholar
  200. 200.
    Barlesi F, Scherpereel A, Gorbunova V, et al. Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous nonsmall-cell lung cancer: updated survival analysis of the AVAPERL (MO22089) randomized phase III trial. Ann Oncol. 2014;25(5):1044–52.PubMedGoogle Scholar
  201. 201.
    Eastern Cooperative Oncology Group. Bevacizumab or pemetrexed disodium alone or in combination after induction therapy in treating patients with advanced non-squamous non-small cell lung cancer [ClinicalTrials.gov identifier NCT01107626] US National Institues of Health, ClinicalTrials.gov. 2012. http://www.clinicaltrials.gov/ct2/show/NCT01107626. Accessed 17 Sep 2014.
  202. 202.
    Seto T, Kato T, Nishio M, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014. doi: 10.1016/S1470-2045(14)70381-X.PubMedGoogle Scholar
  203. 203.
    Wang S-Y. Neoadjuvant pemetrexed, cisplatin and bevacizumab in unresectable, locally advanced lung adenocarcinoma [ClinicalTrials.gov identifier NCT01588704] US National Institues of Health, ClinicalTrials.gov. 2014. http://www.clinicaltrials.gov/ct2/show/NCT01588704. Accessed 17 Sep 2014.
  204. 204.
    National Cancer Institute. Chemotherapy with or without bevacizumab in treating patients with stage IB, stage II, or stage IIIA non-small lung cancer that was removed by surgery [ClinicalTrials.gov identifier NCT00324805] US National Institues of Health, ClinicalTrials.gov. 2014. http://www.clinicaltrials.gov/ct2/show/NCT00324805. Accessed 17 Sep 2014.
  205. 205.
    Hellmann MD, Chaft JE, Rusch V, et al. Risk of hemoptysis in patients with resected squamous cell and other high-risk lung cancers treated with adjuvant bevacizumab. Cancer Chemother Pharmacol. 2013;72(2):453–61.PubMedPubMedCentralGoogle Scholar
  206. 206.
    Lee-Ying R, Lester R, Heng DYC. Current management and future perspectives of metastatic renal cell carcinoma. Int J Urol. 2014;21(9):847–55.PubMedGoogle Scholar
  207. 207.
    National Comprehensive Cancer Network. NCCN clinical practice guidlines in oncology (NCCN guidelines). Kidney cancer: version 1.2015. 2014. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 17 Sep 2014.
  208. 208.
    Diamond E, Riches J, Faltas B, et al. Immunologics and chemotherapeutics for renal cell carcinoma. Semin Intervent Radiol. 2014;31(1):91–7.PubMedPubMedCentralGoogle Scholar
  209. 209.
    Escudier B, Albiges L, Sonpavde G. Optimal management of metastatic renal cell carcinoma: current status. Drugs. 2013;73(5):427–38.PubMedGoogle Scholar
  210. 210.
    Escudier B, Eisen T, Porta C, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):765–71.Google Scholar
  211. 211.
    Halabi S, Rini B, Escudier B, et al. Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma. Cancer. 2014;120(1):52–60.PubMedGoogle Scholar
  212. 212.
    Mickisch GHJ, Schwander B, Escudier B, et al. Indirect treatment comparison of bevacizumab + interferon-alpha-2a vs tyrosine kinase inhibitors in first-line metastatic renal cell carcinoma therapy. ClinicoEcon Out Res. 2011;3:19–27.Google Scholar
  213. 213.
    McDermott DF, George DJ. Bevacizumab as a treatment option in advanced renal cell carcinoma: an analysis and interpretation of clinical trial data. Cancer Treat Rev. 2010;36(3):216–23.PubMedGoogle Scholar
  214. 214.
    M.D. Anderson Cancer Center. Sequential two-agent assessment in renal cell carcinoma therapy: the START trial [ClinicalTrials.gov identifier NCT01217931] US National Institues of Health, ClinicalTrials.gov. 2014. http://www.clinicaltrials.gov/ct2/show/NCT01217931. Accessed 17 Sep 2014.
  215. 215.
    Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349(5):427–34.PubMedPubMedCentralGoogle Scholar
  216. 216.
    Rini BI, Bellmunt J, Clancy J, et al. Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa and bevacizumab in metastatic renal cell carcinoma: INTORACT trial. J Clin Oncol. 2014;32(8):752–9.PubMedGoogle Scholar
  217. 217.
    Négrier S, Gravis G, Pérol D, et al. Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomised phase 2 trial. Lancet Oncol. 2011;12(7):673–80.PubMedGoogle Scholar
  218. 218.
    Ravaud A, Barrios C, Anak Ö, et al. Randomized phase II study of first-line everolimus (EVE) + bevacizumab versus interferon alfa-2a (IFN) + IFN in patients (pts) with metastatic renal cell carcinoma (mRCC): RECORD-2 [abstract no. 7830]. Ann Oncol. 2012;23(Suppl 9):9258.Google Scholar
  219. 219.
    Feldman DR, Baum MS, Ginsberg MS, et al. Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(9):1432–9.PubMedPubMedCentralGoogle Scholar
  220. 220.
    Cardoso F, Harbeck N, Fallowfield L, et al. Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):711–9.Google Scholar
  221. 221.
    European Medicines Agency. Avastin (bevacizumab): EPAR summary for the public. 2012. http://www.ema.europa.eu. Accessed 17 Sep 2014.
  222. 222.
    Lenzer J. FDA committee votes to withdraw bevacizumab for breast cancer. BMJ. 2011;343:d4244.PubMedGoogle Scholar
  223. 223.
    National Comprehensive Cancer Network. NCCN clinical practice guidlines in oncology (NCCN guidelines). Breast cancer: version 3.2014. 2014. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 17 Sep.
  224. 224.
    Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363(20):1938–48.PubMedGoogle Scholar
  225. 225.
    Gligorov J, Doval D, Bines J, et al. Efficacy and safety of maintenance bevacizumab (BEV) with or without capecitabine (CAP) after intiial first-line BEV plus docetaxel (DOC) for HER2-negative metastatic breast cancer (mBC): IMELDA randomised phase III trial [abstract]. In: European Society for Medical Oncology 2014 Congress; 2014; 26–30 Sep 2014; Madrid.Google Scholar
  226. 226.
    von Minckwitz G, Puglisi F, Cortes J, et al. Efficacy and safety in TANIA, a randomised phase III trial of continued or reintroduced bevacizumab (BEV) after 1st-line BEV for HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) [abstract]. In: European Society for Medical Oncology 2014 Congress; 26–30 Sep 2014; Madrid.Google Scholar
  227. 227.
    National Cancer Institute. First-line chemotherapy and trastuzumab with or without bevacizumab in treating patients with metastatic breast cancer that overexpresses HER-2/NEU [ClinicalTrials.gov identifier NCT00520975] US National Institues of Health, ClinicalTrials.gov. 2014. http://www.clinicaltrials.gov/ct2/show/NCT00520975. Accessed 17 Sep 2014.
  228. 228.
    Hoffman-La Roche. A study of Avastin (bevacizumab) in combination with Herceptin (trastuzumab)/docetaxel in patients with HER2 positive metastatic breast cancer [ClinicalTrials.gov identifier NCT00391092] US National Institues of Health, ClinicalTrials.gov. 2014. http://www.clinicaltrials.gov/ct2/show/NCT00391092. Accessed 17 Sep 2014.
  229. 229.
    Spanish Breast Cancer Research Group. Bevacizumab + endocrine treatment vs endocrine treatment as first line treatment in postmenopausal patients with advanced or metastatic breast cancer [ClinicalTrials.gov identifier NCT00545077] US National Institues of Health, ClinicalTrials.gov. 2012. http://www.clinicaltrials.gov/ct2/show/NCT00545077. Accessed 17 Sep 2014.
  230. 230.
    von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366(4):299–309.Google Scholar
  231. 231.
    Bear HD, Tang G, Rastogi P, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366(4):310–20.PubMedPubMedCentralGoogle Scholar
  232. 232.
    Earl HM, Hiller L, Blenkinsop C, et al. ARTesmis: a randomised trial of bevacizumab with neoadjuvant chemotherapy (NACT) for patients with HER2-negative early breast cancer: primary endpoint, pathological complete response (pCR) [abstract no. 1014]. In: 2014 ASCO Annual Meeting; 30 May–3 Jun 2014; Chicago (IL).Google Scholar
  233. 233.
    Gerber B, Loibl S, Eidtmann H, et al. Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the GeparQuinto study (GBG 44). Ann Oncol. 2013;24(12):2978–84.PubMedGoogle Scholar
  234. 234.
    Gerber B, von Minckwitz G, Eidtmann H, et al. Surgical outcome after neoadjuvant chemotherapy and bevacizumab: results from the GeparQuinto study (GBG 44). Ann Surg Oncol. 2014;21(8):2517–24.PubMedGoogle Scholar
  235. 235.
    Slamon DJ, Swain SM, Buyse M, et al. Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2-positive, node-positive or high risk node-negative breast cancer [abstract no. S1-03 plus slide presentation]. In: 36th Annual San Antonio Breast Cancer Symposium; 10–14 Dec 2013; San Antonio (TX).Google Scholar
  236. 236.
    Ledermann JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):624–32.Google Scholar
  237. 237.
    Genentech. Avastin (bevacizumab) solution for intravenous infusion: US prescribing information. 2013. http://www.avastin.com/. Accessed 17 Sep 2014.
  238. 238.
    National Comprehensive Cancer Network. NCCN clinical practice guidlines in oncology (NCCN guidelines). Ovarian cancer including fallopian tube cancer and primary peritoneal cacner: version 3.2014. 2014. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 17 Sep 2014.
  239. 239.
    Monk BJ, Pujade-Lauraine E, Burger RA. Integrating bevacizumab into the management of epithelial ovarian cancer: the controversy of front-line versus recurrent disease. Ann Oncol. 2013;24(Suppl 10):x53–8.PubMedGoogle Scholar
  240. 240.
    Liu JF, Cannistra SA. Emerging role for bevacizumab in combination with chemotherapy for patients with platinum-resistant ovarian cancer. J Clin Oncol. 2014;32(13):1287–9.PubMedGoogle Scholar
  241. 241.
    Eli Lilly and Company. Study of participants with advanced non-small cell lung cancer [ClinicalTrials.gov identifier NCT00948675] US National Institues of Health, ClinicalTrials.gov. 2014. http://www.clinicaltrials.gov/ct2/show/study/NCT00948675. Accessed 17 Sep 2014.

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations