Current Oncology Reports

, 16:404 | Cite as

Optimal Treatment for Metastatic Bladder Cancer

  • Estrella M. Carballido
  • Jonathan E. Rosenberg
Invited Commentary


Metastatic bladder cancer is a lethal disease. Cisplatin-based chemotherapy, including the combination regimens gemcitabine–cisplatin and methotrexate–vinblastine–doxorubicin–cisplatin, are the standard first-line therapies. Second-line therapies have modest activity and no significant improvement in patient outcomes. Agents targeting growth, survival, and proliferation pathways have been added to cytotoxic therapy with limited added benefit to date. Modulating host immune response to cancer-associated antigens appears promising, with multiple new therapeutic approaches being pursued. Next-generation sequencing of invasive urothelial carcinoma has provided insights into the biology of this disease and potential actionable targets. Alterations in the receptor tyrosine kinase/Ras pathway and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway represent potential therapeutic targets in advanced disease, and novel agents are in development. Recent data from the Cancer Genome Atlas Research Network bladder cancer cohort and other efforts suggest that mutations in chromatin-regulatory genes are very common in invasive bladder tumors, and are more frequent than in other studied tumors. The discovery of new genomic alterations challenges drug development to change the course of this disease.


Metastatic bladder cancer Urothelial carcinoma Immunotherapeutics Molecular markers Targeted therapies 



Protein kinase B


Cytotoxic T lymphocyte antigen 4


Epidermal growth factor receptor


Fibroblast growth factor receptor


Gemcitabine and cisplatin


Muscle-invasive bladder cancer


Mammalian target of rapamycin


Methotrexate, vinblastine, doxorubicin, and cisplatin


Phosphatidylinositol 3-kinase


Receptor tyrosine kinase


The Cancer Genome Atlas


Urothelial carcinoma


Vascular endothelial growth factor


Compliance with Ethics Guidelines

Conflict of Interest

Estrella M. Carballido and Jonathan E. Rosenberg declare that they have no conflict of interest

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–66.PubMedCrossRefGoogle Scholar
  3. 3.
    Von Der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18(17):3068–77.PubMedGoogle Scholar
  4. 4.
    Dash A, Pettus JA, Herr HW, Bochner BH, Dalbagni G, Donat SM, et al. A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer. 2008;113(9):2471–7.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006;42(1):50–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, et al. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC intergroup study 30987. J Clin Oncol. 2012;30(10):1107–13.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.•
    Iyer G, Al-Ahmadie H, Schultz N, Hanrahan AJ, Ostrovnaya I, Balar AV, et al. Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol. 2013;31(25):3133–40. This discusses the prevalence and co-occurrence of actionable genomic alterations in high-grade UC. This study highlights that most bladder tumors harbor genomic alterations that may predict response to target agents.PubMedCrossRefGoogle Scholar
  9. 9.
    Gui Y, Guo G, Huang Y, Hu X, Tang A, Gao S, et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat Genet. 2011;43(9):875–8.PubMedCrossRefGoogle Scholar
  10. 10.•
    The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507(7492):315–22. This study describes in depth novel insights into disease biology and the potential clinical significance of recurrent molecular alterations in MIBC. Mutations in epigenetic pathways were frequently seen in UC, suggesting the role of targeting chromatin modifications for treatment of the subset of bladder.CrossRefGoogle Scholar
  11. 11.
    Sternberg CN, Yagoda A, Scher HI, Watson RC, Ahmed T, Weiselberg LR, et al. Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium. J Urol. 1985;133(3):403–7.PubMedGoogle Scholar
  12. 12.
    Sternberg CN, de Mulder PH, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer protocol no. 30924. J Clin Oncol. 2001;19(10):2638–46.PubMedGoogle Scholar
  13. 13.
    Galsky MD, Hahn NM, Rosenberg J, Sonpavde G, Hutson T, Oh WK, et al. Treatment of patients with metastatic urothelial cancer "unfit" for cisplatin-based chemotherapy. J Clin Oncol. 2011;29(17):2432–8.PubMedCrossRefGoogle Scholar
  14. 14.
    De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012;30(2):191–9.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Galsky MD, Iasonos A, Mironov S, Scattergood J, Boyle MG, Bajorin DF. Phase II trial of dose-dense doxorubicin plus gemcitabine followed by paclitaxel plus carboplatin in patients with advanced urothelial carcinoma and impaired renal function. Cancer. 2007;109(3):549–55.PubMedCrossRefGoogle Scholar
  16. 16.
    Hussain M, Vaishampayan U, Du W, Redman B, Smith DC. Combination paclitaxel, carboplatin, and gemcitabine is an active treatment for advanced urothelial cancer. J Clin Oncol. 2001;19(9):2527–33.PubMedGoogle Scholar
  17. 17.
    Vaughn DJ, Malkowicz SB, Zoltick B, Mick R, Ramchandani P, Holroyde C, et al. Paclitaxel plus carboplatin in advanced carcinoma of the urothelium: an active and tolerable outpatient regimen. J Clin Oncol. 1998;16(1):255–60.PubMedGoogle Scholar
  18. 18.
    Dreicer R, Manola J, Roth BJ, See WA, Kuross S, Edelman MJ, et al. Phase III trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium. Cancer. 2004;100(8):1639–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Akdogan B, Dogan HS, Eskicorapci SY, Sahin A, Erkan I, Ozen H. Prognostic significance of bladder tumor history and tumor location in upper tract transitional cell carcinoma. J Urol. 2006;176(1):48–52.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee JLLS, Choi YJ, Ahn JH, Song C, Hong BS, et al. PECULIAR study: phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer. J Clin Oncol. 2014;32(4 Suppl):301.Google Scholar
  21. 21.
    Sweeney CJ, Roth BJ, Kabbinavar FF, Vaughn DJ, Arning M, Curiel RE, et al. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006;24(21):3451–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Vaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002;20(4):937–40.PubMedCrossRefGoogle Scholar
  23. 23.
    McCaffrey JA, Hilton S, Mazumdar M, Sadan S, Kelly WK, Scher HI, et al. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol. 1997;15(5):1853–7.PubMedGoogle Scholar
  24. 24.
    Galsky MD, Mironov S, Iasonos A, Scattergood J, Boyle MG, Bajorin DF. Phase II trial of pemetrexed as second-line therapy in patients with metastatic urothelial carcinoma. Investig New Drugs. 2007;25(3):265–70.CrossRefGoogle Scholar
  25. 25.
    Benjamin DJ BR, Chaim J, Zabor EC, Ostrovnaya I, Garcia-Grossman IR, et al. Efficacy of single-agent pemetrexed in platinum refractory metastatic urothelial cancer. J Clin Oncol. 2014;32(4 Suppl):322.Google Scholar
  26. 26.
    Ko YJ, Canil CM, Mukherjee SD, Winquist E, Elser C, Eisen A, et al. Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study. Lancet Oncol. 2013;14(8):769–76.PubMedCrossRefGoogle Scholar
  27. 27.
    Lorusso V, Pollera CF, Antimi M, Luporini G, Gridelli C, Frassineti GL, et al. A phase II study of gemcitabine in patients with transitional cell carcinoma of the urinary tract previously treated with platinum. Italian Co-operative Group on Bladder Cancer. Eur J Cancer. 1998;34(8):1208–12.PubMedCrossRefGoogle Scholar
  28. 28.
    Witte RS, Elson P, Bono B, Knop R, Richardson RR, Dreicer R, et al. Eastern Cooperative Oncology Group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma. J Clin Oncol. 1997;15(2):589–93.PubMedGoogle Scholar
  29. 29.
    Pronzato PVA, Pensa F, et al. Second line chemotherapy with ifosfamide as outpatient treatment for advanced bladder cancer. Am J Clin Oncol. 1997;20(5):519–21.PubMedCrossRefGoogle Scholar
  30. 30.
    Winquist E, Vokes E, Moore MJ, Schumm LP, Hoving K, Stadler WM. A Phase II study of oxaliplatin in urothelial cancer. Urol Oncol. 2005;23(3):150–4.PubMedCrossRefGoogle Scholar
  31. 31.
    Bellmunt J, Fougeray R, Rosenberg JE, von der Maase H, Schutz FA, Salhi Y, et al. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Ann Oncol. 2013;24(6):1466–72.PubMedCrossRefGoogle Scholar
  32. 32.
    DI Quinn AA, Tsao-Wei DD, et al. Phase II study of eribulin (E7389) in patients (pts) with advanced urothelial cancer (UC): final report: a California Cancer Consortium-led NCI/CTEP-sponsored trial. J Clin Oncol. 2010;28(15 Suppl):4529.Google Scholar
  33. 33.
    Yang CC, Chu KC, Yeh WM. The expression of vascular endothelial growth factor in transitional cell carcinoma of urinary bladder is correlated with cancer progression. Urol Oncol. 2004;22(1):1–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Nguyen PL, Swanson PE, Jaszcz W, Aeppli DM, Zhang G, Singleton TP, et al. Expression of epidermal growth factor receptor in invasive transitional cell carcinoma of the urinary bladder. A multivariate survival analysis. Am J Clin Pathol. 1994;101(2):166–76.PubMedGoogle Scholar
  35. 35.
    Philips GK, Halabi S, Sanford BL, Bajorin D, Small EJ. A phase II trial of cisplatin, fixed dose-rate gemcitabine and gefitinib for advanced urothelial tract carcinoma: results of the Cancer and Leukaemia Group B 90102. BJU Int. 2008;101(1):20–5.PubMedGoogle Scholar
  36. 36.
    Petrylak DP, Tangen CM, Van Veldhuizen PJ, Jr GJW, Twardowski PW, Atkins JN, et al. Results of the Southwest Oncology Group phase II evaluation (study S0031) of ZD1839 for advanced transitional cell carcinoma of the urothelium. BJU Int. 2010;105(3):317–21.PubMedCrossRefGoogle Scholar
  37. 37.
    Grivas PAN, Siefker-Radtke AO, Daignault S, Puzanov I, MacVicar GR, et al. Randomized phase II trial of gemcitabine/cisplatin (GC) with or without cetuximab (CET) in patients (pts) with advanced urothelial carcinoma (UC). J Clin Oncol. 2012;30(15):4506.Google Scholar
  38. 38.
    Wong YN, Litwin S, Vaughn D, Cohen S, Plimack ER, Lee J, et al. Phase II trial of cetuximab with or without paclitaxel in patients with advanced urothelial tract carcinoma. J Clin Oncol. 2012;30(28):3545–51.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Hussain M, Daignault S, Agarwal N, Grivas PD, Siefker-Radtke AO, Puzanov I, et al. A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma. Cancer. 2014. doi: 10.1002/cncr.2876.Google Scholar
  40. 40.
    Wester K, Sjostrom A, de la Torre M, Carlsson J, Malmstrom PU. HER-2—a possible target for therapy of metastatic urinary bladder carcinoma. Acta Oncol. 2002;41(3):282–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Tetu B, Fradet Y, Allard P, Veilleux C, Roberge N, Bernard P. Prevalence and clinical significance of HER/2neu, p53 and Rb expression in primary superficial bladder cancer. J Urol. 1996;155(5):1784–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Fleischmann A, Rotzer D, Seiler R, Studer UE, Thalmann GN. Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours. Eur Urol. 2011;60(2):350–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Wulfing C, Machiels JP, Richel DJ, Grimm MO, Treiber U, De Groot MR, et al. A single-arm, multicenter, open-label phase 2 study of lapatinib as the second-line treatment of patients with locally advanced or metastatic transitional cell carcinoma. Cancer. 2009;115(13):2881–90.PubMedCrossRefGoogle Scholar
  44. 44.
    Daugaard GSL, Agerbaek M, Sternberg CN, Van Herpen C, Collette S, et al. Phase I results from a study of lapatinib with gemcitabine and cisplatin (GC) in advanced/metastatic bladder cancer. J Clin Oncol. 2013;31(6 Suppl):252.Google Scholar
  45. 45.
    Hussain MH, MacVicar GR, Petrylak DP, Dunn RL, Vaishampayan U, Lara PN Jr, et al. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. J Clin Oncol. 2007;25(16):2218–24.Google Scholar
  46. 46.
    Milowsky MIDC, Duran Martinez I, Jagdev S, Millard FE, Sweeney C, et al. Final results of a multicenter, open-label phase II trial of dovitinib (TKI258) in patients with advanced urothelial carcinoma with either mutated or nonmutated FGFR3. J Clin Oncol. 2013;31(6 Suppl):255.Google Scholar
  47. 47.
    Williams SV, Hurst CD, Knowles MA. Oncogenic FGFR3 gene fusions in bladder cancer. Hum Mol Genet. 2013;22(4):795–803.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Kopparapu PK, Boorjian SA, Robinson BD, Downes M, Gudas LJ, Mongan NP, et al. Expression of VEGF and its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer. Anticancer Res. 2013;33(6):2381–90.PubMedGoogle Scholar
  49. 49.
    Bellmunt J, Gonzalez-Larriba JL, Prior C, Maroto P, Carles J, Castellano D, et al. Phase II study of sunitinib as first-line treatment of urothelial cancer patients ineligible to receive cisplatin-based chemotherapy: baseline interleukin-8 and tumor contrast enhancement as potential predictive factors of activity. Ann Oncol. 2011;22(12):2646–53.PubMedCrossRefGoogle Scholar
  50. 50.
    Gallagher DJ, Milowsky MI, Gerst SR, Ishill N, Riches J, Regazzi A, et al. Phase II study of sunitinib in patients with metastatic urothelial cancer. J Clin Oncol. 2010;28(8):1373–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Sridhar SS, Winquist E, Eisen A, Hotte SJ, McWhirter E, Tannock IF, et al. A phase II trial of sorafenib in first-line metastatic urothelial cancer: a study of the PMH Phase II Consortium. Investig New Drugs. 2011;29(5):1045–9.CrossRefGoogle Scholar
  52. 52.
    Necchi A, Mariani L, Zaffaroni N, Schwartz LH, Giannatempo P, Crippa F, et al. Pazopanib in advanced and platinum-resistant urothelial cancer: an open-label, single group, phase 2 trial. Lancet Oncol. 2012;13(8):810–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Galsky MD, Hahn NM, Powles T, Hellerstedt BA, Lerner SP, Gardner TA, et al. Gemcitabine, Cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscle-invasive bladder cancer. Clin Genitourin Cancer. 2013;11(2):175–81.PubMedCrossRefGoogle Scholar
  54. 54.
    Srinivas SNS, Harshman LC, Lam AP, Vaishampayan UN, Haas D, et al. Phase II trial of pazopanib and weekly paclitaxel in metastatic urothelial cancer (UC). J Clin Oncol. 2014;32(4 Suppl 4):299.Google Scholar
  55. 55.
    Balar AV, Apolo AB, Ostrovnaya I, Mironov S, Iasonos A, Trout A, et al. Phase II study of gemcitabine, carboplatin, and bevacizumab in patients with advanced unresectable or metastatic urothelial cancer. J Clin Oncol. 2013;31(6):724–30.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Hahn NM, Stadler WM, Zon RT, Waterhouse D, Picus J, Nattam S, et al. Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoosier Oncology Group GU 04–75. J Clin Oncol. 2011;29(12):1525–30.PubMedCrossRefGoogle Scholar
  57. 57.
    Siefker-Radtke AOKA, Corn PG, Matin SF, Grossman HB, Millikan RE, et al. Neoadjuvant chemotherapy with DD-MVAC and bevacizumab in high-risk urothelial cancer: Results from a phase II trial at the M. D. Anderson Cancer Center. J Clin Oncol. 2012;30(5 Suppl):261.Google Scholar
  58. 58.
    Sorbellini MMB, Simpson H, Giubellino A, Hsieh T, Getzenberg RH, et al. Correlation of Met expression in TCC of the bladder with stage and grade. J Clin Oncol. 2010;28(15 Suppl):e15110.Google Scholar
  59. 59.
    Borghese Apolo APH, Amrit Madan R, Gulley JL, Wright JJ, Hoffman-Censits JH, et al. A phase II study of cabozantinib in patients (pts) with relapsed or refractory metastatic urothelial carcinoma (mUC). J Clin Oncol. 2014;32(4 Suppl 4):307.Google Scholar
  60. 60.
    Munster PSJ, Werner TL, Dees EC, Tan A, Schellens J, et al. PI3K kinase inhibitor GSK2126458 (GSK458): clinical activity in select patient (pt) populations defined by predictive markers. Ann Oncol. 2012;23 Suppl 9:Abstr 4420.Google Scholar
  61. 61.
    Chiong E, Lee IL, Dadbin A, Sabichi AL, Harris L, Urbauer D, et al. Effects of mTOR inhibitor everolimus (RAD001) on bladder cancer cells. Clin Cancer Res. 2011;17(9):2863–73.PubMedCrossRefGoogle Scholar
  62. 62.
    Seront E, Rottey S, Sautois B, Kerger J, D'Hondt LA, Verschaeve V, et al. Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers. Ann Oncol. 2012;23(10):2663–70.PubMedCrossRefGoogle Scholar
  63. 63.
    Milowsky MI, Iyer G, Regazzi AM, Al-Ahmadie H, Gerst SR, Ostrovnaya I, et al. Phase II study of everolimus in metastatic urothelial cancer. BJU Int. 2013;112(4):462–70.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 63.•
    Iyer G, Hanrahan AJ, Milowsky MI, Al-Ahmadie H, Scott SN, Janakiraman M, et al. Genome sequencing identifies a basis for everolimus sensitivity. Science. 2012;338(6104):221. This article describes how whole-genome sequencing was useful to identify a biomarker of drug sensitivity in a patient who experienced durable remission of metastatic UC after treatment with everolimus. A somatic mutation in TSC1 in this case correlated with everolimus sensitivity.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Wagle N, Grabiner BC, Van Allen EM, Hodis E, Jacobus S, Supko JG, et al. Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib. Cancer Discov. 2014;4(5):546–53.PubMedCrossRefGoogle Scholar
  66. 66.
    Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Carthon BC, Wolchok JD, Yuan J, Kamat A, Ng Tang DS, Sun J, et al. Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res. 2010;16(10):2861–71.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Hajdenberg JLD, Vaena DA, Fishman MN, Rosser CJ, Milhem MM, et al. Early outcome results of a phase I/II study for an IL-2/T-cell receptor fusion protein in combination with gemcitabine and cisplatin (GC) in patients with locally advanced or metastatic urothelial cancer. J Clin Oncol. 2012;30(5 Suppl):e15010.Google Scholar
  69. 69.
    Powles T, Vogelzang NJ, Fine GD, Eder JP, Braiteh FS, Loriot Y, et al. Inhibition of PD-L1 by MPDL3280A and clinical activity in pts with metastatic urothelial bladder cancer (UBC). J Clin Oncol. 2014;32(Suppl; abstr 5011):5s.Google Scholar
  70. 70.
    Cha EKSJ, Al-Ahmadie H, Scott SN, Kim PH, Iyer G, et al. Branched evolution and intratumor heterogeneity of urothelial carcinoma of the bladder. J Clin Oncol. 2014;32(4 Suppl):293.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Estrella M. Carballido
    • 1
  • Jonathan E. Rosenberg
    • 2
    • 3
  1. 1.Division of Hematology and Medical OncologyMayo Clinic Cancer CenterScottsdaleUSA
  2. 2.Genitourinary Oncology Service, Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.Weill Cornell Medical CollegeNew YorkUSA

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