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Clinical and Translational Oncology

, Volume 21, Issue 3, pp 280–288 | Cite as

Beyond first-line systemic treatment for metastatic urothelial carcinoma of the bladder

  • E. El Rassy
  • T. AssiEmail author
  • Z. Bakouny
  • N. Pavlidis
  • J. Kattan
Review Article

Abstract

Metastatic urothelial carcinoma of the bladder is a rarely curable disease. Patients receive systemic therapy with limited response rates and survival benefits. The rescue regimens of these patients who have failed first-line treatment had remained problematic until the recent advances. Several trials with novel regimens, including immune checkpoint inhibitors and targeted therapy, to salvage relapsed urothelial carcinoma of the bladder have recently been published. However, the choice of an optimal treatment regimen remains challenging in the absence of randomized trials comparing regimen sequences. Daily clinical cases provoke the question of whether there is a preferred second-line regimen. This paper provides an overview of recent trials and proposes a management algorithm based on subgroup analyses and prognostic features.

Keywords

Urothelial bladder cancer Second-line Chemotherapy Immune checkpoint inhibitor Targeted therapy 

Abbreviations

mUCB

Metastatic urothelial carcinoma of the bladder

GC

Gemcitabine plus cisplatin

MVAC

Methotrexate, vinblastine, doxorubicin and cisplatin

ORR

Overall response rate

PFS

Progression free survival

OS

Overall survival

ICI

Immune checkpoint inhibitor

FDA

Food and drug administration

EMA

European Medicines Agency

HR

Hazard ratio

95% CI

95% confidence interval

QoL

Quality of life

Notes

Compliance with Ethical Standards

Conflict of interest

The authors declares that they have no conflict of interest.

Ethical approval

An approval of the institutional ethics board of the Faculty of Medicine of Saint Joseph University was obtained.

Research involving human participants and/or animals

None.

Informed consent

None.

References

  1. 1.
    Alfred Witjes J, Lebret T, Compérat EM, Cowan NC, De Santis M, Bruins HM, et al. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol. 2017;71(3):462–75.CrossRefGoogle Scholar
  2. 2.
    Salah S, Lee J-L, Rozzi A, Kitamura H, Matsumoto K, Vis DJ, et al. Second-line chemotherapy in older patients with metastatic urothelial carcinoma: pooled analysis of 10 second-line studies. Clin Genitourin Cancer. 2017;15(4):e563–71.CrossRefGoogle Scholar
  3. 3.
    Sonpavde G, Pond GR, Choueiri TK, Mullane S, Niegisch G, Albers P, et al. Single-agent taxane versus taxane-containing combination chemotherapy as salvage therapy for advanced urothelial carcinoma. Eur Urol. 2016;69(4):634–41.CrossRefGoogle Scholar
  4. 4.
    Raggi D, Miceli R, Sonpavde G, Giannatempo P, Mariani L, Galsky MD, et al. Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis. Ann Oncol Off J Eur Soc Med Oncol. 2016;27(1):49–61.CrossRefGoogle Scholar
  5. 5.
    Galsky MD, Hahn NM, Rosenberg JE, Sonpavde G, Oh WK, Dreicer R, et al. Defining “cisplatin ineligible” patients with metastatic bladder cancer. J Clin Oncol. 2011;29(7_suppl):238.CrossRefGoogle Scholar
  6. 6.
    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 Off J Am Soc Clin Oncol. 2005;23(21):4602–8.CrossRefGoogle Scholar
  7. 7.
    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 Oxf Engl 1990. 2006;42(1):50–4.Google Scholar
  8. 8.
    Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, et al. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol Off J Am Soc Clin Oncol. 1990;8(6):1050–5.CrossRefGoogle Scholar
  9. 9.
    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 Off J Am Soc Clin Oncol. 2000;18(17):3068–77.CrossRefGoogle Scholar
  10. 10.
    Sonpavde G, Sternberg CN, Rosenberg JE, Hahn NM, Galsky MD, Vogelzang NJ. Second-line systemic therapy and emerging drugs for metastatic transitional-cell carcinoma of the urothelium. Lancet Oncol. 2010;11(9):861–70.CrossRefGoogle Scholar
  11. 11.
    Yafi FA, North S, Kassouf W. First- and second-line therapy for metastatic urothelial carcinoma of the bladder. Curr Oncol Tor Ont. 2011;18(1):e25–34.Google Scholar
  12. 12.
    Oing C, Rink M, Oechsle K, Seidel C, von Amsberg G, Bokemeyer C. Second line chemotherapy for advanced and metastatic urothelial carcinoma: vinflunine and beyond-A comprehensive review of the current literature. J Urol. 2016;195(2):254–63.CrossRefGoogle Scholar
  13. 13.
    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 Off J Am Soc Clin Oncol. 2012;30(2):191–9.CrossRefGoogle Scholar
  14. 14.
    Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet Lond Engl. 2017;389(10):67–76.CrossRefGoogle Scholar
  15. 15.
    Balar A, Bellmunt J, O’Donnell PH, Castellano D, Grivas P, Vuky J, et al. Pembrolizumab (pembro) as first-line therapy for advanced/unresectable or metastatic urothelial cancer: preliminary results from the phase 2 KEYNOTE-052 study. Ann Oncol. 2016;27(suppl 6):LBA32_PR.Google Scholar
  16. 16.
    Aoun F, Rassy EE, Assi T, Albisinni S, Katan J. Advances in urothelial bladder cancer immunotherapy, dawn of a new age of treatment. Immunotherapy. 2017;9(5):451–60.CrossRefGoogle Scholar
  17. 17.
    Sonpavde G. PD-1 and PD-L1 inhibitors as salvage therapy for urothelial carcinoma. N Engl J Med. 2017;376(11):1073–4.CrossRefGoogle Scholar
  18. 18.
    Sonpavde G, Jones BS, Bellmunt J, Choueiri TK, Sternberg CN. Future directions and targeted therapies in bladder cancer. Hematol Clin. 2015;29(2):361–76.CrossRefGoogle Scholar
  19. 19.
    Bellmunt J, Théodore C, Demkov T, Komyakov B, Sengelov L, Daugaard G, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(27):4454–61.CrossRefGoogle Scholar
  20. 20.
    Culine S, Theodore C, De Santis M, Bui B, Demkow T, Lorenz J, et al. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer. 2006;94(10):1395–401.CrossRefGoogle Scholar
  21. 21.
    Vaughn DJ, Srinivas S, Stadler WM, Pili R, Petrylak D, Sternberg CN, et al. Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: results of a large phase 2 study. Cancer. 2009;115(18):4110–7.CrossRefGoogle Scholar
  22. 22.
    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 Off J Eur Soc Med Oncol. 2013;24(6):1466–72.CrossRefGoogle Scholar
  23. 23.
    Vaughn DJ, Manola J, Dreicer R, See W, Levitt R, Wilding G. Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896): a trial of the Eastern Cooperative Oncology Group. Cancer. 2002;95(5):1022–7.CrossRefGoogle Scholar
  24. 24.
    Papamichael D, Gallagher CJ, Oliver RT, Johnson PW, Waxman J. Phase II study of paclitaxel in pretreated patients with locally advanced/metastatic cancer of the bladder and ureter. Br J Cancer. 1997;75(4):606–7.CrossRefGoogle Scholar
  25. 25.
    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 Off J Am Soc Clin Oncol. 1997;15(5):1853–7.CrossRefGoogle Scholar
  26. 26.
    Powles T, Durán I, van der Heijden MS, Loriot Y, Vogelzang NJ, Giorgi UD, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. The Lancet. 2018;391(10122):748–57.CrossRefGoogle Scholar
  27. 27.
    Petrylak D, Vogelzang NJ, Fradet Y, Bajorin D, de Wit R, Vaughn DJ, et al. 851PDSubgroup analyses from KEYNOTE-045: Pembrolizumab (pembro) versus individual investigator’s choice of chemotherapy (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (uc). Ann Oncol [Internet]. 2017;28(suppl_5). https://academic.oup.com/annonc/article/28/suppl_5/mdx371.006/4108937. Accessed 18 Sept 2017.
  28. 28.
    Han KS, Joung JY, Kim TS, Jeong IG, Seo HK, Chung J, et al. Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy. Br J Cancer. 2008;98(1):86–90.CrossRefGoogle Scholar
  29. 29.
    Fechner G, Siener R, Reimann M, Kobalz L, Albers P, German Association Of Urologic Oncology (Auo) Bladder Cancer Study Group. Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO Trial AB 20/99). Int J Clin Pract. 2006;60(1):27–31.CrossRefGoogle Scholar
  30. 30.
    Albers P, Park S-I, Niegisch G, Fechner G, Steiner U, Lehmann J, et al. Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99]. Ann Oncol Off J Eur Soc Med Oncol. 2011;22(2):288–94.CrossRefGoogle Scholar
  31. 31.
    Dreicer R. Second-line chemotherapy for advanced urothelial cancer: because we should or because we can? J Clin Oncol. 2009;27(27):4444–5.CrossRefGoogle Scholar
  32. 32.
    Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. The Lancet. 2016;387(10031):1909–20.CrossRefGoogle Scholar
  33. 33.
    Sharma P, Callahan MK, Bono P, Kim J, Spiliopoulou P, Calvo E, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016;17(11):1590–8.CrossRefGoogle Scholar
  34. 34.
    O’Donnell PH, Grivas P, Balar AV, Bellmunt J, Vuky J, Powles T, et al. Biomarker findings and mature clinical results from KEYNOTE-052: first-line pembrolizumab (pembro) in cisplatin-ineligible advanced urothelial cancer (UC). J Clin Oncol. 2017;35(15_suppl):4502.CrossRefGoogle Scholar
  35. 35.
    Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee J-L, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376(11):1015–26.CrossRefGoogle Scholar
  36. 36.
    Rassy EE, Bakouny Z, Aoun F, Haddad FG, Sleilaty G, Assi T, et al. A network meta-analysis of the PD(L)-1 inhibitors in the salvage treatment of urothelial bladder cancer. Immunotherapy [Internet]. 2018. https://www.futuremedicine.com/doi/10.2217/imt-2017-0190. Accessed 22 Mar 2018.
  37. 37.
    Vaughn DJ, Bellmunt J, Fradet Y, Lee JL, Fong L, Vogelzang NJ, et al. Health-related quality-of-life analysis from KEYNOTE-045: a Phase III study of pembrolizumab versus chemotherapy for previously treated advanced urothelial cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2018 Mar 28;JCO2017769562.Google Scholar
  38. 38.
    Martini DJ, Lalani A-KA, Bossé D, Steinharter JA, Harshman LC, Hodi FS, et al. Response to single agent PD-1 inhibitor after progression on previous PD-1/PD-L1 inhibitors: a case series. J Immunother Cancer. 2017;5(1):66.CrossRefGoogle Scholar
  39. 39.
    Kim JM, Chen DS. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Ann Oncol Off J Eur Soc Med Oncol. 2016;27(8):1492–504.CrossRefGoogle Scholar
  40. 40.
    Necchi A, Joseph RW, Loriot Y, Hoffman-Censits J, Perez-Gracia JL, Petrylak DP, et al. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study. Ann Oncol Off J Eur Soc Med Oncol. 2017;28(12):3044–50.CrossRefGoogle Scholar
  41. 41.
    Bellmunt J, De Wit R, Vaughn DJ, Fradet Y, Lee J-L, Fong L, et al. Two-year follow-up from the phase 3 KEYNOTE-045 trial of pembrolizumab (pembro) vs investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC). J Clin Oncol. 2018;36(6_suppl):410–410.CrossRefGoogle Scholar
  42. 42.
    Anagnostou V, Yarchoan M, Hansen AR, Wang H, Verde F, Sharon E, et al. Immuno-oncology trial endpoints: capturing clinically meaningful activity. Clin Cancer Res Off J Am Assoc Cancer Res. 2017;23(17):4959–69.CrossRefGoogle Scholar
  43. 43.
    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 Off J Am Soc Clin Oncol. 2010;28(8):1373–9.CrossRefGoogle Scholar
  44. 44.
    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.CrossRefGoogle Scholar
  45. 45.
    Petrylak DP, de Wit R, Chi KN, Drakaki A, Sternberg CN, Nishiyama H, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial. Lancet Lond Engl. 2017;390(10109):2266–77.CrossRefGoogle Scholar
  46. 46.
    Necchi A, Nishiyama H, Matsubara N, Lee J-L, Petrylak DP, De Wit R, et al. Quality-of-life (QoL) in RANGE: A phase 3 study of ramucirumab (RAM) plus docetaxel (DOC) versus placebo (P) plus DOC in platinum-refractory locally advanced or metastatic urothelial carcinoma (UC). J Clin Oncol. 2018;36(6_suppl):419.CrossRefGoogle Scholar
  47. 47.
    Gomez de Liano Lista A, Necchi A, Lavaud P, Carles Galceran J, Castellano D, Ravaud A, et al. 862PTreatment and outcome after Immune checkpoint inhibitors (ICI) in metastatic Urothelial Carcinoma (mUC): a European perspective. Ann Oncol [Internet]. 2017;28(suppl_5). https://academic.oup.com/annonc/article/28/suppl_5/mdx371.016/4108947. Accessed 18 Sept 2017.
  48. 48.
    Sonpavde G, Pond GR, Rosenberg JE, Bajorin DF, Choueiri TK, Necchi A, et al. Improved 5-factor prognostic classification of patients receiving salvage systemic therapy for advanced urothelial carcinoma. J Urol. 2016;195(2):277–82.CrossRefGoogle Scholar
  49. 49.
    Pond GR, Sonpavde G, Galsky MD, Sharma P, Rosenberg JE, Choueiri TK, et al. Nivolumab demonstrates benefit over nomogram-predicted 12-month survival as salvage therapy for metastatic urothelial carcinoma. J Clin Oncol. 2018;36(6_suppl):451.CrossRefGoogle Scholar
  50. 50.
    Pond GR, Niegisch G, Rosenberg JE, Dreicer R, Powles T, Necchi A, et al. New 6-factor prognostic model for patients (pts) with advanced urothelial carcinoma (UC) receiving post-platinum atezolizumab. J Clin Oncol. 2018;36(6):413.CrossRefGoogle Scholar
  51. 51.
    Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507(7492):315–22.CrossRefGoogle Scholar
  52. 52.
    Choi W, Porten S, Kim S, Willis D, Plimack ER, Hoffman-Censits J, et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 2014;25(2):152–65.CrossRefGoogle Scholar
  53. 53.
    McConkey DJ, Choi W, Shen Y, Lee I-L, Porten S, Matin SF, et al. A prognostic gene expression signature in the molecular classification of chemotherapy-naïve urothelial cancer is predictive of clinical outcomes from neoadjuvant chemotherapy: a Phase 2 trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with bevacizumab in urothelial cancer. Eur Urol. 2016;69(5):855–62.CrossRefGoogle Scholar
  54. 54.
    Choudhury NJ, Campanile A, Antic T, Yap KL, Fitzpatrick CA, Wade JL, et al. Afatinib activity in platinum-refractory metastatic urothelial carcinoma in patients with ERBB alterations. J Clin Oncol. 2016;34(18):2165–71.CrossRefGoogle Scholar
  55. 55.
    Wülfing C, Machiels J-PH, Richel DJ, Grimm M-O, Treiber U, Groot MRD, 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.CrossRefGoogle Scholar
  56. 56.
    Javle MM, Shroff RT, Zhu A, Sadeghi S, Choo S, Borad MJ, et al. A phase 2 study of BGJ398 in patients (pts) with advanced or metastatic FGFR-altered cholangiocarcinoma (CCA) who failed or are intolerant to platinum-based chemotherapy. J Clin Oncol. 2016;34(4_suppl):335.CrossRefGoogle Scholar
  57. 57.
    Bellmunt J, Pal SK, Picus J, Kohli M, Arriaga YE, Milowsky MI, et al. Safety and efficacy of docetaxel + b-701, a selective inhibitor of FGFR3, in subjects with advanced or metastatic urothelial carcinoma. J Clin Oncol. 2017;35(15_suppl):4540.CrossRefGoogle Scholar
  58. 58.
    Tang K, Jiang K, Zhou H, Liu H, Ye Z, Xu H. MP78-09 Predictive And Prognostic Role Of PD-L1 IN urothelial carcinoma patients with anti-PD-1/PD-L1 therapy: a systematic review and meta-analysis. J Urol. 2018;199(4):e1040.Google Scholar
  59. 59.
    Dadhania V, Zhang M, Zhang L, Bondaruk J, Majewski T, Siefker-Radtke A, et al. Meta-analysis of the luminal and basal subtypes of bladder cancer and the identification of signature immunohistochemical markers for clinical use. EBioMedicine. 2016;25(12):105–17.CrossRefGoogle Scholar
  60. 60.
    Pond GR, Bellmunt J, Fougeray R, Choueiri TK, Qu AQ, Niegisch G, et al. Impact of response to prior chemotherapy in patients with advanced urothelial carcinoma receiving second-line therapy: implications for trial design. Clin Genitourin Cancer. 2013;11(4):495–500.CrossRefGoogle Scholar
  61. 61.
    Rozzi A, Santini D, Salerno M, Bordin F, Mancuso A, Minniti G, et al. Pegylated liposomal doxorubicin as third-line chemotherapy in patients with metastatic transitional cell carcinoma of urothelial tract: results of a phase II study. Med Oncol Northwood Lond Engl. 2013;30(1):407.CrossRefGoogle Scholar
  62. 62.
    Soga N, Kise H, Arima K, Sugimura Y. Third-line gemcitabine monotherapy for platinum-resistant advanced urothelial cancer. Int J Clin Oncol. 2010;15(4):376–81.CrossRefGoogle Scholar
  63. 63.
    Naiki T, Iida K, Kawai N, Etani T, Ando R, Nagai T, et al. A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma. J Rural Med JRM. 2017;12(2):105–11.CrossRefGoogle Scholar
  64. 64.
    Matsumoto K, Mochizuki K, Hirayama T, Ikeda M, Nishi M, Tabata K, et al. Gemcitabine plus nedaplatin as salvage therapy is a favorable option for patients with progressive metastatic urothelial carcinoma after two lines of chemotherapy. Asian Pac J Cancer Prev APJCP. 2015;16(6):2483–7.CrossRefGoogle Scholar
  65. 65.
    Di Lorenzo G, Buonerba C, Bellelli T, Romano C, Montanaro V, Ferro M, et al. Third-line chemotherapy for metastatic urothelial cancer: a retrospective observational study. Medicine (Baltimore) [Internet]. 2015;94(51). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697979/. Accessed 28 Dec 2015.
  66. 66.
    Rassy EE, Kourie HR, Rizkallah J, Karak FE, Hanna C, Chelala DN, et al. Immune checkpoint inhibitors renal side effects and management. Immunotherapy. 2016;8(12):1417–25.CrossRefGoogle Scholar
  67. 67.
    Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, et al. Hyperprogressive disease (HPD) is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res. 2016;23(8):1920–8.CrossRefGoogle Scholar
  68. 68.
    Joseph RW, Loriot Y, Perez-Gracia JL, Dreicer R, Petrylak DP, van der Heijden MS, et al. MP78-07 clinical characteristics associated with early progression or long-term response from the phase II IMVIGOR210 study: atezolizumab in locally advanced or metastatic urothelial carcinomA. J Urol. 2018;199(4):e1039.Google Scholar
  69. 69.
    Allen E, Jabouille A, Rivera LB, Lodewijckx I, Missiaen R, Steri V, Feyen K, Tawney J, Hanahan D, Michael IP, Bergers G. Combined antiangiogenic and anti–PD-L1 therapy stimulates tumor immunity through HEV formation. Sci Transl Med. 2017;.  https://doi.org/10.1126/scitranslmed.aak9679.Google Scholar
  70. 70.
    Petrylak DP, Arkenau H-T, Perez-Gracia JL, Krebs M, Santana-Davila R, Yang J, et al. A multicohort phase I study of ramucirumab (R) plus pembrolizumab (P): Interim safety and clinical activity in patients with urothelial carcinoma. J Clin Oncol. 2017;35(6):349.CrossRefGoogle Scholar
  71. 71.
    Petrylak DP, Perez RP, Zhang J, Smith DC, Ruether JD, Sridhar SS, et al. A phase I study of enfortumab vedotin (ASG-22CE; ASG-22ME): Updated analysis of patients with metastatic urothelial cancer. J Clin Oncol. 2017;35(15_suppl):106.CrossRefGoogle Scholar
  72. 72.
    Sharma P, Callahan MK, Calvo E, et al. Efficacy and safety of nivolumab plus ipilimumab in previously treated metastatic urothelial carcinoma: First results from the phase I/II CheckMate 032 study. In: Presented at: 2016 SITC annual meeting; November 9–13, 2016; National Harbor, MD.Google Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Department of Medical Oncology, Faculty of Medicine, Hotel Dieu de France University HospitalSaint Joseph UniversityBeirutLebanon
  2. 2.Department of Medical Oncology, Institut Gustave RoussyUniversité Paris-SaclayVillejuifFrance
  3. 3.University of IoanninaIoanninaGreece

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