Inmunoterapia en Cáncer Vesical. Presente y Futuro

Palabras clave: tumor vesical, inmunoterapia, tratamientos, musculo invasivo, no musculo invasivo

Resumen

El cáncer vesical (BC) continúa siendo un reto en la práctica clínica urológica actual. Es el séptimo tumor más frecuente diagnosticado en varones a nivel mundial y el 11º si tenemos en cuenta ambos sexos.

Ya desde el abordaje del tumor vesical no músculo invasivo (NMIBC) existen limitaciones en el tratamiento: resección transuretral no siempre completa, fracasos o recidivas precoces tras el tratamiento con BCG así como efectos secundarios que obligan a la suspensión de la misma.

En el tratamiento del tumor vesical músculo invasivo (MIBC) la cistectomía radical no es una opción para todos los pacientes debido a la importante comorbilidad perioperatoria. En los pacientes con tumores vesicales metastásicos, los efectos secundarios de la quimioterapia convencional, así como la progresión tumoral, ha suscitado una necesidad de desarrollar nuevas líneas terapéuticas.

Los avances en el conocimiento de la biología molecular oncológica, han posibilitado encontrar nuevas dianas terapéuticas (como los inhibidores del ciclo celular) y mediante el empleo de anticuerpos monoclonales, desarrollar fármacos específicos dirigidos contra ellas. Actualmente hay cinco fármacos aprobados por la FDA y la EMA para el tratamiento en el cáncer vesical musculoinvasivo metastásico, entre los cuales destacan atezolizumab, nivolumab y pembrolizumab por su mayor implantación en la práctica clínica.

Los buenos resultados obtenidos en el cáncer vesical metastásico, han provocado el desarrollo de nuevas líneas de investigación para el empleo de estas moléculas en estadíos más precoces de la enfermedad y en protocolos de neoadyuvancia. Así mismo, se están realizando múltiples estudios sobre la combinación de estos nuevos agentes con quimioterapia convencional y radioterapia para determinar los esquemas de tratamiento más adecuados.

En este trabajo recogemos de manera sucinta el estado actual de la inmunoterapia en el cáncer vesical.

Citas

Brausi M, Collette L, Kurth K, van der Meijden AP, Oosterlinck W, Witjes JA, et al. Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: a combined analysis of seven EORTC studies. Eur Urol. 2002;41(5):523–31. doi: 10.1016/s0302-2838(02)00068-4

Cumberbatch MGK, Foerster B, Catto JWF, Kamat AM, Kassouf W, Jubber I, et al. Repeat Transurethral Resection in Non-muscle-invasive Bladder Cancer: A Systematic Review. Eur Urol. 2018;73(6):925–33. doi: 10.1016/j.eururo.2018.02.014

Naselli A, Hurle R, Paparella S, Buffi NM, Lughezzani G, Lista G, et al. Role of Restaging Transurethral Resection for T1 Non-muscle invasive Bladder Cancer: A Systematic Review and Meta-analysis. Eur Urol Focus. 2018;4(4):558–67. doi: 10.1016/j.euf.2016.12.011

Grimm M-O, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, Vogeli TA. Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study. J Urol. 2003;170(2 Pt 1):433–7. doi: 10.1097/01.ju.0000070437.14275.e0

.

Sylvester RJ, van der MEIJDEN APM, Lamm DL. Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol. 2002;168(5):1964–70. doi: 10.1097/01.ju.0000034450.80198.1c

Witjes JA. Management of BCG failures in superficial bladder cancer: a review. Eur Urol. 2006 May;49(5):790–7. doi: 10.1016/j.eururo.2006.01.017

Steinberg RL, Thomas LJ, Mott SL, O’Donnell MA. Bacillus Calmette-Guérin (BCG) Treatment Failures with Non-Muscle Invasive Bladder Cancer: A Data-Driven Definition for BCG Unresponsive Disease. Bladder Cancer. 2016;2(2):215–24. doi: 10.3233/BLC-150039

Nathenson MJ, Conley AP, Sausville E. Immunotherapy: A New (and Old) Approach to Treatment of Soft Tissue and Bone Sarcomas. Oncologist. 2018;23(1):71–83. doi: 10.1634/theoncologist.2016-0025

Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480–9. doi: 10.1038/nature10673

Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10. doi: 10.1016/j.immuni.2013.07.012

Doyle E, Crew J, Mostafid H, Tuthill M, Cerundolo V, Gerristen W, et al. Urothelial cancer: a narrative review of the role of novel immunotherapeutic agents with particular reference to the management of non-muscle-invasive disease. BJU Int. 2019;123(6):947–58. doi: 10.1111/bju.14643

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. Lancet. 2016;387(10031):1909–20. doi: 10.1016/S0140-6736(16)00561-4

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. 2017;389(10064):67–76. doi: 10.1016/S0140-6736(16)32455-2

Powles T, Durán I, van der Heijden MS, Loriot Y, Vogelzang NJ, De Giorgi U, 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. Lancet. 2018;391(10122):748–57. doi: 10.1016/S0140-6736(17)33297-X

Gabriele A. Comunicación dirigida a profesionales sanitarios Cotellic® (Cobimetinib): Advertencias Adicionales en relación con el riesgo de hemorragia y Rabdomiólisis. Nuevas recomendaciones de Modificación de dosis. España: Roche Farma S.A.; 2017.

Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18(3):312–22. doi: 10.1016/S1470-2045(17)30065-7

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. New England Journal of Medicine. 2017;376(11):1015–26. doi: 10.1056/NEJMoa1613683

Jokisch J-F, Karl A, Stief C. Intravesical immunotherapy in nonmuscle invasive bladder cancer. Indian J Urol. 2015;31(4):304–11. doi: 10.4103/0970-1591.166452

Glashan RW. A randomized controlled study of intravesical alpha-2b-interferon in carcinoma in situ of the bladder. J Urol. 1990;144(3):658–61. doi: 10.1016/s0022-5347(17)39547-2

Shepherd AR, Shepherd E, Brook NR. Intravesical Bacillus Calmette-Guérin with interferon-alpha versus intravesical Bacillus Calmette-Guérin for treating non-muscle-invasive bladder cancer. Cochrane Database Syst Rev. 2017;3:CD012112. doi: 10.1002/14651858.CD012112.pub2

Lamm D, Brausi M, O’Donnell MA, Witjes JA. Interferon alfa in the treatment paradigm for non-muscle-invasive bladder cancer. Urol Oncol. 2014;32(1):35. e21-30. doi: 10.1016/j.urolonc.2013.02.010

Morales A, Herr H, Steinberg G, Given R, Cohen Z, Amrhein J, et al. Efficacy and safety of MCNA in patients with nonmuscle invasive bladder cancer at high risk for recurrence and progression after failed treatment with bacillus Calmette-Guérin. J Urol. 2015;193(4):1135–43. doi: 10.1016/j.juro.2014.09.109

Morales A. Evolution of intravesical immunotherapy for bladder cancer: mycobacterial cell wall preparation as a promising agent. Expert Opinion on Investigational Drugs. 2008;17(7):1067–73. doi: 10.1517/13543784.17.7.1067

National Library of Medicine. Novel Therapeutic Approaches for Recurrent Non Muscle invasive Bladder Cancer. Clinical Trials.gov. [accessed 3 Oct 2020] Available from: https://www.clinicaltrials.gov/ct2/results?cond=Novel+Therapeutic+Approaches+for+Recurrent+Non+Muscle+invasive+Bladder+Cancer&term=&cntry=&state=&city=&dist=

Newton MR, Askeland EJ, Andresen ED, Chehval VA, Wang X, Askeland RW, et al. Anti-interleukin-10R1 monoclonal antibody in combination with bacillus Calmette--Guérin is protective against bladder cancer metastasis in a murine orthotopic tumour model and demonstrates systemic specific anti-tumour immunity. Clin Exp Immunol. 2014;177(1):261–8. doi: 10.1111/cei.12315

Malmström P-U, Agrawal S, Bläckberg M, Boström PJ, Malavaud B, Zaak D, et al. Non-muscle-invasive bladder cancer: a vision for the future. Scand J Urol. 2017;51(2):87–94. doi: 10.1080/21681805.2017.1283359

Autenrieth M, Kurtz F, Horn T, Seidl C, Morgenstern A, Bruchertseifer F, et al. Intravesikale α-Strahler-Radioimmuntherapie mit Bi-213-anti-EGFR-mAb beim Carcinoma in situ-Rezidiv nach BCG-Therapie: eine Alternative zur Zystektomie? In German Medical Science GMS Publishing House; 2015. p. DocFV06. doi: 10.3205/15oegu06

Powles T, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Font Pous A, et al. A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in muscle invasive bladder cancer (ABACUS). JCO. 2018;36(15_suppl):4506–4506. doi: 10.1200/JCO.2018.36.15_suppl.4506

Necchi A, Briganti A, Bianchi M, Raggi D, Giannatempo P, Luciano’ R, et al. Preoperative pembrolizumab (pembro) before radical cystectomy (RC) for muscle-invasive urothelial bladder carcinoma (MIUC): Interim clinical and biomarker findings from the phase 2 PURE-01 study. JCO. 2018;36(15_suppl):4507–4507. doi: 10.1200/JCO.2018.36.15_suppl.4507

Joerger M, Cassier P, Penel N, Cathomas R, Richly H, Schostak M, et al. Rogaratinib treatment of patients with advanced urothelial carcinomas prescreened for tumor FGFR mRNA expression. JCO. 2018;36(6_suppl):494–494. doi: 10.1200/JCO.2018.36.6_suppl.494

Siefker-Radtke AO, Necchi A, Park SH, GarcÃa-Donas J, Huddart RA, Burgess EF, et al. First results from the primary analysis population of the phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRalt). JCO. 2018;36(15_suppl):4503–4503. doi: 10.1200/JCO.2018.36.15_suppl.4503

Rosenberg JE, Sridhar SS, Zhang J, Smith DC, Ruether JD, Flaig TW, et al. Updated results from the enfortumab vedotin phase 1 (EV-101) study in patients with metastatic urothelial cancer (mUC). JCO. 2018;36(15_suppl):4504–4504. doi: 10.1200/JCO.2018.36.15_suppl.4504

Bajwa R, Cheema A, Khan T, Amirpour A, Paul A, Chaughtai S, et al. Adverse Effects of Immune Checkpoint Inhibitors (Programmed Death-1 Inhibitors and Cytotoxic T-Lymphocyte-Associated Protein-4 Inhibitors): Results of a Retrospective Study. Journal of Clinical Medicine Research. 2019;11(4):225–36. doi: 10.14740/jocmr3750

Choi J, Lee SY. Clinical Characteristics and Treatment of Immune-Related Adverse Events of Immune Checkpoint Inhibitors. Immune Network. 2020;20(1):e9. doi: 10.4110/in.2020.20.e9

Wanchoo R, Karam S, Uppal NN, Barta VS, Deray G, Devoe C, et al. Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review. American Journal of Nephrology. 2017;45(2):160–9. doi: 10.1159/000455014

Diem S, Keller F, Rüesch R, Maillard SA, Speiser DE, Dummer R, Siano M, Urner-Bloch U, Goldinger SM, Flatz L. Pembrolizumab-triggered Uveitis: An Additional Surrogate Marker for Responders in Melanoma Immunotherapy? J Immunother. 2016 Nov/Dec;39(9):379-382. doi: 10.1097/CJI.0000000000000143. PMID: 27662340.

Schuler M, Cho BC, Sayehli CM, Navarro A, Soo RA, Richly H, et al. Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study. The Lancet Oncology. 2019;20(10):1454–66. doi: 10.1016/S1470-2045(19)30412-7

Poza del Val, M et al. Actualización de la inmunoterapia en cáncer de Vejiga.Futuro. En: Lorenzo Gómez Mf, editor. Memoria Urológica San Zoilo VI. Salamanca.2019 p 37-54

Publicado
2021-01-13
Sección
Artículos de revisión