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Risk of Treatment-related Mortality with Sorafenib in Patients with Cancer

  • Zhang, Xin-Ji (Department of Health Statistics, Second Military Medical University) ;
  • Zhang, Tian-Yi (Department of Health Statistics, Second Military Medical University) ;
  • Yu, Fei-Fei (Department of Health Statistics, Second Military Medical University) ;
  • Wei, Xin (Renji Hospital, Shanghai Jiao Tong University School of Medicine) ;
  • Li, Ye-Sheng (Department of Special Treatment, Eastern Hepatobiliary Hospital, Second Military Medical University) ;
  • Xu, Feng (Department of Special Treatment, Eastern Hepatobiliary Hospital, Second Military Medical University) ;
  • Wei, Li-Xin (Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Hospital, Second Military Medical University) ;
  • He, Jia (Department of Health Statistics, Second Military Medical University)
  • Published : 2013.11.30

Abstract

Background: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. Methods: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. Results: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). Conclusions: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.

Keywords

Sorafenib;epidermal growth factor receptor-2;fatal adverse events;mortality;meta-analysis

References

  1. Abou-Alfa GK, Johnson P, Knox JJ, et al (2010). Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA, 304, 2154-60. https://doi.org/10.1001/jama.2010.1672
  2. 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
  3. Baselga J, Segalla JG, Roche H, et al (2012). Sorafenib in combination with capecitabine: an oral regimen for patients with HER2-negative locally advanced or metastatic breast cancer. J Clin Oncol, 30, 1484-91. https://doi.org/10.1200/JCO.2011.36.7771
  4. 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
  5. Bennett CL, Silver SM, Djulbegovic B, et al (2008). Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA, 299, 914-24. https://doi.org/10.1001/jama.299.8.914
  6. Byrne AM, Bouchier-Hayes DJ, Harmey JH (2005). Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med, 9, 777-94. https://doi.org/10.1111/j.1582-4934.2005.tb00379.x
  7. Cheng AL, Kang YK, Chen Z, et al (2009). Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol, 10, 25-34. https://doi.org/10.1016/S1470-2045(08)70285-7
  8. 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
  9. Chu D, Lacouture ME, Fillos T, Wu S (2008). Risk of hand-foot skin reaction with sorafenib: a systematic review and meta-analysis. Acta Oncol, 47, 176-86. https://doi.org/10.1080/02841860701765675
  10. 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
  11. Deeks JJ, Higgins J, Altman DG (2008). Analysing Data and Undertaking Meta-Analyses. Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series, 243-96.
  12. Egger M, Smith GD, 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
  13. Escudier B, Eisen T, Stadler WM, et al (2007). Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med, 356, 125-34. https://doi.org/10.1056/NEJMoa060655
  14. Escudier B, Eisen T, Stadler WM, et al (2009). Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol, 27, 3312-8. https://doi.org/10.1200/JCO.2008.19.5511
  15. Escudier B, Szczylik C, Hutson TE, et al (2009). Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol, 27, 1280-9. https://doi.org/10.1200/JCO.2008.19.3342
  16. Esmon CT (1987). The regulation of natural anticoagulant pathways. Science, 235, 1348-52. https://doi.org/10.1126/science.3029867
  17. Ewer MS, Suter TM, Lenihan DJ, et al (2010). Cardiovascular adverse events (CV-AES) in a pooled analysis of 1090 patients (PT) from phase 3 suntinib (SU) trials. 35th European Society for Medical Oncology. Milan, Italy, 506.
  18. Flaherty KT, Lee SJ, Zhao F, et al (2013). Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma. J Clin Oncol, 31, 373-9. https://doi.org/10.1200/JCO.2012.42.1529
  19. Galal KM, Khaled Z, Mourad AM (2011). Role of cetuximab and sorafenib in treatment of metastatic colorectal cancer. Indian J Cancer, 48, 47-54. https://doi.org/10.4103/0019-509X.75825
  20. Gonzalez-Pacheco FR, Deudero JJ, Castellanos MC, et al (2006). Mechanisms of endothelial response to oxidative aggression: protective role of autologous VEGF and induction of VEGFR2 by H2O2. Am J Physiol Heart Circ Physiol, 291, H1395-401. https://doi.org/10.1152/ajpheart.01277.2005
  21. Hauschild A, Agarwala SS, Trefzer U, et al (2009). Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol, 27, 2823-30. https://doi.org/10.1200/JCO.2007.15.7636
  22. Hutson T, Procopio G, Escudier B, et al (2010). Long-term sorafenib (SOR) safety profile in more than 700 patients (pts) with renal-cell carcinoma (RCC) treated for 12 to 42 months (mos). J Clin Oncol (Meeting Abstracts).
  23. Jadad AR, Moore RA, Carroll D, et al (1996). Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 17, 1-12. https://doi.org/10.1016/0197-2456(95)00134-4
  24. 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
  25. Kamba T, McDonald DM (2007). Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer, 96, 1788-95. https://doi.org/10.1038/sj.bjc.6603813
  26. Kerkela R, Woulfe KC, Durand JB, et al (2009). Sunitinib-induced cardiotoxicity is mediated by off-target inhibition of AMP-activated protein kinase. Clin Transl Sci, 2, 15-25. https://doi.org/10.1111/j.1752-8062.2008.00090.x
  27. Kim ES, Herbst RS, Wistuba II, et al (2011). The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov, 1, 44-53. https://doi.org/10.1158/2159-8274.CD-10-0010
  28. Kudo M, Imanaka K, Chida N, et al (2011). Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer, 47, 2117-27. https://doi.org/10.1016/j.ejca.2011.05.007
  29. Llovet JM, Ricci S, Mazzaferro V, et al (2008). Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 359, 378-90. https://doi.org/10.1056/NEJMoa0708857
  30. McDermott DF, Sosman JA, Gonzalez R, et al (2008). Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group. J Clin Oncol, 26, 2178-85. https://doi.org/10.1200/JCO.2007.14.8288
  31. Muszbek N, Shah S, Carroll S, et al (2008). Economic evaluation of sorafenib in the treatment of hepatocellular carcinoma in Canada. Curr Med Res Opin, 24, 3559-69. https://doi.org/10.1185/03007990802563706
  32. National Cancer Institute Common Toxicity Criteria (version 2 or 3) (2006). from http://ctepcancergov/protocolDevelopment/electronic_application/ctchtm
  33. Paz-Ares LG, Biesma B, Heigener D, et al (2012). Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol, 30, 3084-92. https://doi.org/10.1200/JCO.2011.39.7646
  34. Printz C (2009). Clinical trials of note. Sorafenib as adjuvant treatment in the prevention of disease recurrence in patients with hepatocellular carcinoma (HCC) (STORM). Cancer, 115, 4646. https://doi.org/10.1002/cncr.24673
  35. Ranpura V, Hapani S, Wu S (2011). Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis. JAMA, 305, 487-94. https://doi.org/10.1001/jama.2011.51
  36. Ratain MJ, Eisen T, Stadler WM, et al (2006). Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol, 24, 2505-12. https://doi.org/10.1200/JCO.2005.03.6723
  37. Rini BI, Escudier B, Tomczak P, et al (2011). Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet, 378, 1931-9. https://doi.org/10.1016/S0140-6736(11)61613-9
  38. Scagliotti G, Novello S, von Pawel J, et al (2010). Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol, 28, 1835-42. https://doi.org/10.1200/JCO.2009.26.1321
  39. Schutz FA, Je Y, Richards CJ, Choueiri TK (2012). Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with cancer treated with vascular endothelial growth factor tyrosine kinase inhibitors. J Clin Oncol, 30, 871-7. https://doi.org/10.1200/JCO.2011.37.1195
  40. Shen BQ, Lee DY, Zioncheck TF (1999). Vascular endothelial growth factor governs endothelial nitric-oxide synthase expression via a KDR/Flk-1 receptor and a protein kinase C signaling pathway. J Biol Chem, 274, 33057-63. https://doi.org/10.1074/jbc.274.46.33057
  41. Sivendran S, Liu Z, Portas LJ, Jr., et al (2012). Treatment-related mortality with vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy in patients with advanced solid tumors: a meta-analysis. Cancer Treat Rev, 38, 919-25. https://doi.org/10.1016/j.ctrv.2012.05.001
  42. Sonpavde G, Bellmunt J, Schutz F, Choueiri TK (2012). The double edged sword of bleeding and clotting from VEGF inhibition in renal cancer patients. Curr Oncol Rep, 14, 295-306. https://doi.org/10.1007/s11912-012-0237-9
  43. Spigel DR, Burris HA, Greco FA, et al (2011). Randomized, double-blind, placebo-controlled, phase II trial of sorafenib and erlotinib or erlotinib alone in previously treated advanced non-small-cell lung cancer. J Clin Oncol, 29, 2582-9. https://doi.org/10.1200/JCO.2010.30.7678
  44. Wang Y, Wang L, Liu Y, et al (2011). Randomize trial of cisplatin plus gemcitabine with either sorafenib or placebo as first-line therapy for non-small cell lung cancer. Zhongguo Fei Ai Za Zhi, 14, 239-44.
  45. Wilhelm SM, Carter C, Tang L, et al (2004). BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res, 64, 7099-109. https://doi.org/10.1158/0008-5472.CAN-04-1443
  46. Wu S, Chen JJ, Kudelka A, Lu J, Zhu X (2008). Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol, 9, 117-23. https://doi.org/10.1016/S1470-2045(08)70003-2
  47. Zachary I, Gliki G (2001). Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res, 49, 568-81. https://doi.org/10.1016/S0008-6363(00)00268-6

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