Zusammenfassung
Das Harnblasenkarzinom ist in seinem fortgeschrittenen und metastasierten Stadium schwierig zu behandeln. Mehrere Faktoren spielen eine Rolle: Alter, Multimorbidität und insbesondere eingeschränkte Nierenfunktion und Neuropathien verhindern in den meisten Fällen eine lebensverlängernde chemotherapeutische Therapie. In der zweiten Linie sind Ansprechraten und Verbesserung vom Gesamtüberleben kaum unterschiedlich zu allgemeinen palliativen Maßnahmen. In den letzten beiden Jahren hat sich die therapeutische Landschaft dramatisch verändert. Immuntherapien, hauptsächlich durch Vertreter der Checkpoint-Inhibitoren, haben durch positive Studienergebnisse die EMA- (European Medicines Agency‑)Zulassungen erlangt. Sowohl in der Zweitlinie nach Platin-haltiger Chemotherapie, als auch als Erstlinientherapie beim unfitten Patienten, können diese Substanzen eingesetzt werden. Neue Konzepte mit Kombinationen aus immuntherapeutisch wirksamen Komponenten werden derzeit in vielen Studien untersucht. Optimismus macht sich breit, wenn man die Daten von anderen Karzinomen (Melanom, nichtkleinzelliges Bronchuskarzinom) verfolgt.
Abstract
Urothelial carcinoma of the bladder is difficult to treat in advanced and metastatic stages. Several factors play a role: age, multimorbidity including impaired renal function and neuropathy make access to life-prolonging chemotherapy impossible in many cases. Improvements of response rates and overall survival in the second-line setting are not much different compared to best supportive care. However, the therapeutic landscape has changed dramatically during the last 2 years. Immunotherapies represented by checkpoint inhibitors have showed positive trial outcomes and have been approved by EMA (European Medicines Agency). Both in second-line therapy after platinum-based chemotherapy and in first-line therapy in unfit patients, these drugs can be used. New concepts with combinations of immunotherapeutic compounds are currently being examined in various trials. If we follow the data of other malignancies (melanoma and non-small cell lung cancer), the future looks optimistic.
Literatur
Siegel RL, Miller KD, Jemal A (2017) Cancer statistics. Ca Cancer J Clin 67:7–30
WHO IARC 2012
Statistik Austria 2017
NCI SEER Data Base: https://seer.cancer.gov/
Galsky MD, Pal SK, Lin SW, Ogale S et al (2018) Real world effectiveness of chemotherapy in elderly patients with bladder cancer in the USA. Bladder Cancer 4(2):227–238
Von der Maase H, Sengelov L, Roberts JT et al (2005) 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 23:4602
Sonpavde G, Galsky MD, Latini D, Chen GJ (2014) Cisplatin-ineligible and chemotherapy-ineligible patients should be the focus of new drug development in patients with advanced bladder cancer. Clin Genitourin Cancer 12(2):71–73
Raggi D, Miceli R, Sonpavde G et al (2016) Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis. Ann Oncol 27:49
Boorijan SA, Sheinin Y, Crispen PL et al (2008) T‑cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathological correlations and association with survival. Clin Cancer Res 14:4800
Nakanishi J, Wada Y, Matsumoto K et al (2007) Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunther 56:1173
McDaniel AS, Alva A, Zhan T et al (2016) Expression of PD-L1 (B7-H1) before and after neoadjuvant chemotherapy in urothelial carcinoma. Eur Urol Focus 1:265
Massard C, Gordon MS, Sharma S et al (2016) Safety and efficacy of durvalumab (MEDI4738), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol 34:3119
Sharma P, Retz M, Siefker-Radtke A et al (2017) Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicenter, single-arm, phase 2 trial. Lancet Oncol 18:312
Rosenberg JE, Hoffman-Censits J, Powles T et al (2016) 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. Lancet 387:1909–1920
Powles T (2017) IMvigor 211: A phase III randomized study examining atezolizumab vs. chemotherapy for platinum-treated advanced urothelial carcinoma. In: EACR-AACR-SIC Special Conference 2017, Florence, 24–27 June 2017.
Powles T, O’Donnell PH, Massard C et al (2017) Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. JAMA Oncol 3:e172411
Apolo AB, Infante JR, Balmanoukian A et al (2017) Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase 1b study. J Clin Oncol 35:2117
Bellmunt J, de Wit R, Vaughn DJ et al (2017) Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376:1015–1026
Sternberg CN, de Mulder P, Schornagel JH et al (2006) Seven year update of an EORTC phase 3 trial of high-dose intensity MVAC chemotherapy plus G‑CSF versus classic MVAC in advanced urothelial tract tumours. Eur J Cancer 42:50–54
Balar AV, Galsky MD, Rosenberg JE et al (2017) Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 389:67–76
De Santis M, Bellmunt J, Mead G et al (2012) 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 30:191–199
O’Donnell PH, Grivas P, Balar AV et al (2017) Biomarker findings and mature clinical results from KEYNOTE-052: first-line pembrolizumab (pembro) in cisplatin-ineligible advanced urothelial cancer (UC). J Clin Oncol 35(15_suppl):4502
Smith DC, Gasewski T, Hamid O et al (2017) Epacadostat plus pembrolizumab in patients with advanced urothelial carcinoma: preliminary phase I/II results of ECHO-202/KEYNOTE-037. J Clin Oncol 35(15_suppl):4503
Hahn NM, Powles T, Massard C et al (2017) Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma (UC). J Clin Oncol 35(Suppl):4525
Patel MR, Ellerton JA, Infante JR et al (2017) Avelumab in patients with metastatic urothelial carcinoma: pooled results from two cohorts of the phase 1b JAVELIN Solid Tumor trial. J Clin Oncol 35(Suppl 6):330. https://doi.org/10.1200/JCO.2017.35.6_suppl.330
Schumacher TN, Schreiber RD (2015) Neoantigens in cancer immuntherapy. Science 348:69
Rizvi NA, Hellman MD, Snyder A et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124
Galsky MD, Saci A, Szabo A et al (2017) Impact of tumor mutational burden on nivolumab efficacy in second-line urothelial carcinoma patients: exploratory analysis of the phase II CheckMate 275 study. Ann Oncol 28(Suppl):848PD
Pal SK, Agarwal N, Boorjian SA et al (2016) National comprehensive cancer network recommendations on molecular profiling of advanced bladder cancer. J Clin Oncol 34:3346–3348
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W. Loidl und F. Luger geben an, an folgender Studie teilgenommen zu haben: Von der Maase H, Sengelov L, Roberts JT 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; 23:4602.
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Loidl, W., Luger, F. Immuntherapie beim lokal fortgeschrittenen und metastasierten Harnblasenkarzinom. Urologe 57, 1334–1341 (2018). https://doi.org/10.1007/s00120-018-0785-1
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DOI: https://doi.org/10.1007/s00120-018-0785-1