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Efficacy and Toxicity of Anti-VEGF Agents in Patients with Castration-Resistant Prostate Cancer: a Meta-analysis of Prospective Clinical Studies

  • Qi, Wei-Xiang (Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center) ;
  • Fu, Shen (Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center) ;
  • Zhang, Qing (Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center) ;
  • Guo, Xiao-Mao (Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center)
  • Published : 2014.10.23

Abstract

Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ${\geq}50%$) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.

Keywords

References

  1. Abou-Alfa GK, Schwartz L, Ricci S, et al (2006). Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol, 24, 4293-300 https://doi.org/10.1200/JCO.2005.01.3441
  2. Aragon-Ching JB, Dahut WL (2009). VEGF inhibitors and prostate cancer therapy. Curr Molec Pharmacol, 2, 161-8 https://doi.org/10.2174/1874467210902020161
  3. Balagula Y, Wu S, Su X, Feldman DR, Lacouture ME (2011). The risk of hand foot skin reaction to pazopanib, a novel multikinase inhibitor: a systematic review of literature and meta-analysis. Invest New Drugs
  4. Beardsley EK, Hotte SJ, North S, et al (2012). A phase II study of sorafenib in combination with bicalutamide in patients with chemotherapy-naive castration resistant prostate cancer. Invest New Drugs, 30, 1652-9 https://doi.org/10.1007/s10637-011-9722-5
  5. Begg CB, Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088-101 https://doi.org/10.2307/2533446
  6. Belum VR, Wu S, Lacouture ME (2013). Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Invest New Drugs
  7. Berthold DR, Pond GR, Soban F, et al (2008). Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol, 26, 242-5 https://doi.org/10.1200/JCO.2007.12.4008
  8. Bok RA, Halabi S, Fei DT, et al (2001). Vascular endothelial growth factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate cancer patients: a cancer and leukemia group B study. Cancer Res, 61, 2533-6
  9. Borre M, Bentzen SM, Nerstrom B, Overgaard J (1998a). Tumor cell proliferation and survival in patients with prostate cancer followed expectantly. J Urol, 159, 1609-14 https://doi.org/10.1097/00005392-199805000-00054
  10. Borre M, Offersen BV, Nerstrom B, Overgaard J (1998b). Microvessel density predicts survival in prostate cancer patients subjected to watchful waiting. Br J Cancer, 78, 940-4 https://doi.org/10.1038/bjc.1998.605
  11. Choueiri TK, Schutz FA, Je Y, Rosenberg JE, Bellmunt J (2010). Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. J Clin Oncol, 28, 2280-5 https://doi.org/10.1200/JCO.2009.27.2757
  12. Chu D, Lacouture ME, Weiner E, Wu S (2009). Risk of hand-foot skin reaction with the multitargeted kinase inhibitor sunitinib in patients with renal cell and non-renal cell carcinoma: a meta-analysis. Clin Genitourin Cancer, 7, 11-9 https://doi.org/10.3816/CGC.2009.n.002
  13. Di Lorenzo G, Figg WD, Fossa SD, et la (2008). Combination of bevacizumab and docetaxel in docetaxel-pretreated hormone-refractory prostate cancer: a phase 2 study. Eur Urol, 54, 1089-94 https://doi.org/10.1016/j.eururo.2008.01.082
  14. Duque JL, Loughlin KR, Adam RM, et al (1999). Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer. Urology, 54, 523-7 https://doi.org/10.1016/S0090-4295(99)00167-3
  15. Egger M, Davey Smith G, Schneider M, Minder C (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ 315, 629-34 https://doi.org/10.1136/bmj.315.7109.629
  16. Eisenberger MA, Walsh PC (1999). Early androgen deprivation for prostate cancer? N Engl J Med, 341, 1837-8 https://doi.org/10.1056/NEJM199912093412409
  17. Ferrara N, Davis-Smyth T (1997). The biology of vascular endothelial growth factor. Endocrine reviews, 18, 4-25 https://doi.org/10.1210/edrv.18.1.0287
  18. Fischer A, Wu S, Ho AL, Lacouture ME (2013). The risk of hand-foot skin reaction to axitinib, a novel VEGF inhibitor: a systematic review of literature and meta-analysis. Invest New Drugs
  19. Folkman J (2002). Role of angiogenesis in tumor growth and metastasis. Seminars in oncology, 29, 15-8
  20. Folkman J (2006). Angiogenesis. Ann Rev Med, 57, 1-18 https://doi.org/10.1146/annurev.med.57.121304.131306
  21. Funakoshi T, Latif A, Galsky MD (2013). Risk of hematologic toxicities in cancer patients treated with sunitinib: A systematic review and meta-analysis. Cancer Treat Rev, 39, 818-30. https://doi.org/10.1016/j.ctrv.2013.01.004
  22. Grothey A, Van Cutsem E, Sobrero A, et al (2013). Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet, 381, 303-12 https://doi.org/10.1016/S0140-6736(12)61900-X
  23. Gustavsson H, Welen K, Damber JE (2005). Transition of an androgen-dependent human prostate cancer cell line into an androgen-independent subline is associated with increased angiogenesis. Prostate, 62, 364-73 https://doi.org/10.1002/pros.20145
  24. Hicklin DJ, Ellis LM (2005). Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol, 23, 1011-27
  25. Hurwitz H, Fehrenbacher L, Novotny W, et la (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med, 350, 2335-42 https://doi.org/10.1056/NEJMoa032691
  26. Je Y, Schutz FA, Choueiri TK (2009). Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. Lancet Oncol, 10, 967-74 https://doi.org/10.1016/S1470-2045(09)70222-0
  27. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90 https://doi.org/10.3322/caac.20107
  28. Jia Y, Lacouture ME, Su X, Wu S (2009). Risk of skin rash associated with erlotinib in cancer patients: a meta-analysis. J Support Oncol, 7, 211-7
  29. Loblaw DA, Walker-Dilks C, Winquist E, Hotte SJ (2013). Systemic therapy in men with metastatic castration-resistant prostate cancer: a systematic review. Clin Oncol, 25, 406-30 https://doi.org/10.1016/j.clon.2013.03.002
  30. Merino M, Pinto A, Gonzalez R, Espinosa E (2011). Antiangiogenic agents and endothelin antagonists in advanced castration resistant prostate cancer. Eur J Cancer, 47, 1846-51 https://doi.org/10.1016/j.ejca.2011.04.020
  31. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF (1999). Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet, 354, 1896-900 https://doi.org/10.1016/S0140-6736(99)04149-5
  32. Motzer RJ, Escudier B, Tomczak P, et al (2013a). Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol, 14, 552-62 https://doi.org/10.1016/S1470-2045(13)70093-7
  33. Motzer RJ, Hutson TE, Cella D, et al (2013b). Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med, 369, 722-31 https://doi.org/10.1056/NEJMoa1303989
  34. Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD (2006). Sunitinib in patients with metastatic renal cell carcinoma. JAMA, 295, 2516-24 https://doi.org/10.1001/jama.295.21.2516
  35. Mukherji D, Temraz S, Wehbe D, Shamseddine A (2013). Angiogenesis and anti-angiogenic therapy in prostate cancer. Crit Rev Oncol Hematol, 87, 122-31 https://doi.org/10.1016/j.critrevonc.2013.01.002
  36. Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S (2008). Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA, 300, 2277-85 https://doi.org/10.1001/jama.2008.656
  37. Perren TJ, Swart AM, Pfisterer J, et al (2011). A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med, 365, 2484-96 https://doi.org/10.1056/NEJMoa1103799
  38. Qi WX, He AN, Shen Z, Yao Y (2013a). Incidence and risk of hypertension with a novel multi-targeted kinase inhibitor axitinib in cancer patients: a systematic review and metaanalysis. Br J Clin Pharmacol, 76, 348-57 https://doi.org/10.1111/bcp.12149
  39. Qi WX, Lin F, Sun YJ, et al (2013b). Incidence and risk of hypertension with pazopanib in patients with cancer: a meta-analysis. Cancer Chemother Pharmacol , 71, 431-9 https://doi.org/10.1007/s00280-012-2025-5
  40. Qi WX, Min DL, Shen Z, et al (2013c). Risk of venous thromboembolic events associated with VEGFR-TKIs: a systematic review and meta-analysis. Int J Cancer, 132, 2967-74 https://doi.org/10.1002/ijc.27979
  41. Qi WX, Shen Z, Lin F, et al (2013d). Incidence and risk of hypertension with vandetanib in cancer patients: a systematic review and meta-analysis of clinical trials. Br J Clin Pharmacol, 75, 919-30 https://doi.org/10.1111/j.1365-2125.2012.04417.x
  42. Qi WX, Shen Z, Tang LN, Yao Y (2014). Risk of hypertension in cancer patients treated with aflibercept: a systematic review and meta-analysis. Clin Drug Investig, 34, 231-40 https://doi.org/10.1007/s40261-014-0174-5
  43. Qi WX, Shen Z, Yao Y (2011a). Docetaxel-based therapy with or without estramustine as first-line chemotherapy for castration-resistant prostate cancer: a meta-analysis of four randomized controlled trials. J Cancer Res Clin Oncol, 137, 1785-90 https://doi.org/10.1007/s00432-011-1052-7
  44. Qi WX, Tang LN, He AN, Shen Z, Yao Y (2011b). The role of vandetanib in the second-line treatment for advanced nonsmall-cell-lung cancer: a meta-analysis of four randomized controlled trials. Lung, 189, 437-43 https://doi.org/10.1007/s00408-011-9332-1
  45. Qi WX, Tang LN, Sun YJ, et al (2013e). Incidence and risk of hemorrhagic events with vascular endothelial growth factor receptor tyrosine-kinase inhibitors: an up-to-date metaanalysis of 27 randomized controlled trials. Ann Oncol, 24, 2943-52 https://doi.org/10.1093/annonc/mdt292
  46. Ryan CJ, Small EJ (2003). Role of secondary hormonal therapy in the management of recurrent prostate cancer. Urology , 62, 87-94 https://doi.org/10.1016/j.urology.2003.10.002
  47. Sandler A, Gray R, Perry MC, et al (2006). Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med, 355, 2542-50 https://doi.org/10.1056/NEJMoa061884
  48. Santoni M, Conti A, De Giorgi U, et al (2013). Risk of gastrointestinal events with sorafenib, sunitinib and pazopanib in patients with solid tumors: A systematic review and meta-analysis of clinical trials. Int J Cancer, 135, 763-73.
  49. Scappaticci FA, Skillings JR, Holden SN, et al (2007). Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst, 99, 1232-9 https://doi.org/10.1093/jnci/djm086
  50. Schutz FA, Jardim DL, Je Y, Choueiri TK (2011a). Haematologic toxicities associated with the addition of bevacizumab in cancer patients. Eur J Cancer, 47, 1161-74 https://doi.org/10.1016/j.ejca.2011.03.005
  51. Schutz FA, Je Y, Choueiri TK (2011b). Hematologic toxicities in cancer patients treated with the multi-tyrosine kinase sorafenib: a meta-analysis of clinical trials. Crit Rev Oncol Hematol, 80, 291-300 https://doi.org/10.1016/j.critrevonc.2010.11.007
  52. Van Cutsem E, Tabernero J, Lakomy R, et al (2012). Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol, 30, 3499-506 https://doi.org/10.1200/JCO.2012.42.8201
  53. Wang K, Peng HL, Li LK (2012). Prognostic value of vascular endothelial growth factor expression in patients with prostate cancer: a systematic review with meta-analysis. Asian Pac J Cancer Prev, 13, 5665-9 https://doi.org/10.7314/APJCP.2012.13.11.5665
  54. Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J (1993). Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol, 143, 401-9
  55. Wu Y, Rosenberg JE, Taplin ME (2011). Novel agents and new therapeutics in castration-resistant prostate cancer. Curr Opin Oncol, 23, 290-6 https://doi.org/10.1097/CCO.0b013e3283449400
  56. Yang JC, Haworth L, Sherry RM, et al (2003). . A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med, 349, 427-34 https://doi.org/10.1056/NEJMoa021491
  57. Zintzaras E, Ioannidis JP (2005). Heterogeneity testing in metaanalysis of genome searches. Genet Epidemiol, 28, 123-37 https://doi.org/10.1002/gepi.20048

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