Bevacizumab based chemotherapy in first line treatment of HER2 negative metastatic breast cancer: results of a Moroccan observational institutional study

BMC Research Notes

Hassan Errihani¹  Saber Boutayeb¹  Lamiaa Boulaamane² 

[1] Department of medical oncology, National institute of oncology, 10100 Rabat, Morocco;Department of Medical Oncology, National Institute of Oncology, Sidi Mohamed Ben Abdellah Hospital, Rabat, Morocco

关键词: Salvage treatment;    Meta-analysis;    Taxanes;    Metastatic breast cancer;    Bevacizumab;   

Others  :  1166556
DOI  :  10.1186/1756-0500-5-162

 received in 2011-10-09, accepted in 2012-03-22,  发布年份 2012

【 摘 要 】

Background

In metastatic breast cancer (MBC) patients, randomised controlled trials evaluated Bevacizumab as first-line treatment showed improvements in tumour response rate and progression-free survival (PFS) when added to chemotherapy. In Morocco, we conducted an observational study to investigate clinical features, treatment and prognosis associated with Bevacizumab based chemotherapy in first line treatment of HER2 negative MBC.

Findings

Nineteen women were included in this study. All these women were diagnosed as having HER2 negative MBC at the National Institute of Oncology in Rabat, Morocco, between January 2009 and December 2010. The median age of patients was 48.1 years. Four patients (21%) had metastatic disease at diagnosis and 15 patients (79%) had received treatment for first metastatic relapse. Bone, liver and lung were the most frequent metastasis sites. Patients were followed up until April 2011. Most patients had objective response; 15.8% of complete response, 47.3% of partial response and 21.1% of stabilisation. Median PFS was estimated at 11.5 months. Sub-groups analysis showed a statistically significant difference (Log-rank test: p = 0.01); PFS for patients receiving Bevacizumab - weekly Paclitaxel was estimated at 18.1 months, and at 9.1 months for patients receiving the combination Bevacizumab - Docetaxel. This benefit in PFS was associated with an acceptable safety profile.

Conclusion

As demonstrated in this study, Bevacizumab based chemotherapy in first line treatment of HER2 negative MBC in Morocco and particularly in combination with Taxanes extends PFS, as confirmed in a recent meta-analysis of 3 randomised controlled phase III studies.

【 授权许可】

   
2011 Boulaamane et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Pal SK, Gupta R, Somlo G, Hurria A, Chung CT, Luu TH, Bernstein L, Mortimer J: Lack of survival benefit in metastatic breast cancer with newer chemotherapy agents: The City of Hope cancer experience. J Clin Oncol 2008, 26:s20. (abstr 17510)
• [2]Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G: Tumor angiogenesis: a new significant and independent prognostic indicator in earlystage breast carcinoma. J Natl Cancer Inst 1992, 84(24):1875-1887.
• [3]Uzzan B, Nicolas P, Cucherat M, Perret GY: Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and metaanalysis. Cancer Res 2004, 64(9):2941-2955.
• [4]McLeskey SW, Tobias CA, Vezza PR, Filie AC, Kern FG, Hanfelt J: Tumor growth of FGF or VEGF transfected MCF-7 breast carcinoma cells correlates with density of specific microvessels independent of the transfected angiogenic factor. Am J Pathol 1998, 153(6):1993-2006.
• [5]Linderholm B, Grankvist K, Wilking N, Johansson M, Tavelin B, Henriksson R: Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment. J Clin Oncol 2000, 18(7):1423-1431.
• [6]Scott LJ: Bevacizumab: in first-line treatment of metastatic breast cancer. Drugs 2000, 67(12):1793-1799.
• [7]Miller K, Wang D, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NA: Paclitaxel plus bevacizumab versus paclitacel alone for metastatic breast cancer. N Engl J Med 2007, 357:2666-2676.
• [8]Pivot X, Verma S, Thomssen C, Passos-Coelho JL, Latini L, Ciruelos E, Silva M, von Moos R, Chang H, Miles DW: Clinical benefit of bevacizumab plus first-line docetaxel in elderly patients with locally recurrent or Metastatic breast cancer. J Clin Oncol 2009, 27:15s. abstr 1094
• [9]Robert NJ, Dieras V, Glaspy J, Brufsky A, Bondarenko I, Lipatov O, Perez E, Yardley E, Zhou X, Phan S: RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer. J Clin Oncol 2009, 27:15s. abstr 1005
• [10]O'Shaughnessy J, Miles D, Gray RJ, Dieras V, Perez EA, Zon R, Cortes J, Zhou X, Phan S, Miller K: A meta-analysis of overall survival data from three randomized trials of bevacizumab (BV) and first-line chemotherapy as treatment for patients with metastatic breast cancer (MBC). J Clin Oncol 2010, 28:15s. suppl; abstr 1005
• [11]Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med 1971, 285:1182-1186.
• [12]Hicklin DJ, Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005, 23:1011-1027.
• [13]Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Dushyant V, Sahani DV, Kalva SP, Kozin SV, Mino M, Cohen KS, Scadden DT, Alan C, Hartford AC, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Chen HX, Shellito PC, Lauwers GY, Jain RK: Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004, 10:145-147.
• [14]Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD, McDonald DM: Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol 2004, 165:35-52.
• [15]Marty M, Pivot X: The potential of anti-vascular endothelial growth factor therapy in metastatic breast cancer: clinical experience with anti-angiogenic agents, focusing on bevacizumab. Eur J Cancer 2008, 44:912-920.
• [16]Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N: Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumours and other disorders. Cancer Res 1997, 57(20):4593-4599.
• [17]Genentech, Inc: [http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125085s0168lbl.pdf] webciteUS Prescribing Information for Avastin.
• [18]Hoffmann-La Roche Ltd. Avastin Summary of Product Characteristics [http:/ / www.emea.europa.eu/ humandocs/ PDFs/ EPAR/ avastin/ emea-combinedh582en. pdf] webcite
• [19]Belotti D, Vergani V, Drudis T, Borsotti P, Pitelli MR, Viale G, Giavazzi R, Taraboletti G: The microtubule-affecting drug paclitaxel has antiangiogenic activity. Clin Cancer Res 1996, 2(11):1843-1849.
• [20]Sweeney CJ, Miller KD, Sissons SE, Nozaki S, Heilman DK, Shen J, Sledge GW Jr: The antiangiogenic property of docetaxel is synergistic with a recombinant humanized monoclonal antibody against vascular endothelial growth factor or 2-methoxyestradiol but antagonized by endothelial growth factors. Cancer Res 2001, 61(8):3369-3372.
• [21]Gray R, Bhattacharya S, Bowden C, Miller K, Comis RL: Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol 2009, 27:4966-4972.
• [22]Cameron D: Bevacizumab in the first-line treatment of metastatic breast cancer. Eur J Cancer Suppl 2008, 6(6):21-28.
• [23]Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G: Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of HER2- negative metastatic breast cancer. J Clin Oncol 2010, 28(20):3239-3247.
• [24]Klencke B, Bhattacharya S, Samant M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Davidson NE, Miller K: Independent review of E2100 validates progression-free survival (PFS) improvement with the addition of bevacizumab (B) to paclitaxel (P) as initial chemotherapy for metastatic breast cancer (MBC). J Clin Oncol 2008, 26:50s. Abstr 1036
• [25]Miles D, Chan A, Romieu G, Dirix LY, Cortes J, Pivot X, Tomczak P, Taran T, Harbeck N, Steger GG: Randomized, double-blind, placebo controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J Clin Oncol 2008, 26:1008s. Abstr LBA1011
• [26]Gordon MS, Cunningham D: Managing patients treated with bevacizumab combination therapy. Oncology 2005, 69:25-33.