Biomarcadores predictivos de respuesta a los inhibidores de los puntos de control inmunitario
Resumen
Objetivo: El objetivo del presente trabajo es identificar mediante revisión bibliográfica los factores dependientes del tumor que condicionan la respuesta a los inhibidores de los puntos de control inmunitario, incidiendo especialmente en aquellos que se postulan como posibles biomarcadores predictivos.
Método: Búsquedas en Pubmed con los términos biomarkers, PD-1, PD‑L1, CTLA-4, checkpoint inhibitors, en el título o el abstract, seleccionando aquellos que incluyeran información relevante sobre factores tumorales que condicionan la respuesta a los inhibidores de los puntos de control inmunitario. Se priorizaron estudios en humanos (ensayos clínicos y revisiones) publicados entre enero de 2015 y junio de 2019, en idiomas inglés y español.
Resultados: La revisión pone de manifiesto las complejas relaciones entre sistema inmunitario y tumor, con factores que influyen en la respuesta a los inhibidores de los puntos de control inmunitario variados, y aun poco conocidos, lo cual dificulta la obtención de biomarcadores predictivos sencillos y/o universales.
Conclusiones: Actualmente los únicos biomarcadores utilizados en práctica clínica, en algunos escenarios, son la expresión del ligando del receptor de muerte celular programada-1 y la inestabilidad de microsatélites/deficiencias en las enzimas de reparación de los apareamientos erróneos durante la replicación del ácido desoxirribonucleico, aunque su utilidad es limitada. La carga mutacional y las firmas génicas asociadas a interferón gamma se postulan como biomarcadores útiles, una vez sistematizadas las técnicas de determinación y los puntos de corte.
Palabras clave
Referencias
Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv192-237. DOI: 10.1093/annonc/mdy275
Karlsson AK, Saleh SN. Checkpoint inhibitors for malignant melanoma: a systematic review and meta-analysis. Clin Cosmet Investig Dermatol. 2017;10:325-39. DOI: 10.2147/CCID.S120877
Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(5):706-20. DOI:10.1093/annonc/mdw328
Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36(17):1714-68. DOI: 10.1200/JCO.2017.77.6385
Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(Suppl 4):iv119-42. DOI: 10.1093/annonc/mdx22
Chen DS, Mellman I. Elements of cancer immunity and the cancer–immune set point. Nature. 2017;541(7637):321-30. DOI: 10.1038/nature21349
Hegde PS, Karanikas V, Evers S. The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition. Clin Cancer Res. 2016;22(8):1865-74. DOI: 10.1158/1078-0432.CCR-15-1507
Joshi S, Durden DL. Combinatorial approach to improve cancer immunotherapy: Rational drug design strategy to simultaneously hit multiple targets to kill tumor cells and to activate the immune system. J Oncol. 2019;5245034. DOI: 10.1155/2019/5245034
Amin A, Hammers H. The evolving landscape of immunotherapy-based combinations for frontline treatment of advanced renal cell carcinoma. Front Immunol [Internet]. 2019 [accessed 02/07/2019];9:3120. Available at: https://www.frontiersin.org/article/10.3389/fimmu.2018.03120/f ull. DOI: 10.3389/fimmu.2018.03120
Hanna GG, Illidge T. Radiotherapy and immunotherapy combinations in nonsmall cell lung cancer: A promising future? Clin Oncol. 2016;28(11):726-31. DOI: 10.1016/j.clon.2016.07.014
Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, et al. The immune landscape of cancer. Immunity. 2018;48(4):812-830.e14. DOI: 10.1016/j.immuni.2018.03.023
Usó M, Jantus-Lewintre E, Bremnes RM, Calabuig S, Blasco A, Pastor E, et al. Analysis of the immune microenvironment in resected non-small cell lung cancer: the prognostic value of different T lymphocyte markers. Oncotarget [Internet]. 2016 [accessed 01/29/2019];7(33):52849-52861. Available at: http://www.oncotarget.com/fulltext/10811. DOI: 10.18632/oncotarget.10811
Geng Y, Shao Y, He W, Hu W, Xu Y, Chen J, et al. Prognostic role of tumor-infiltrating lymphocytes in lung cancer: A meta- analysis. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 2015;37(4):1560-71. DOI: 10.1159/000438523
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568-71. DOI: 10.1038/nature13954
Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, et al. Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest. 2016;126(9):3447-52. DOI:10.1172/JCI87324
Berger KN, Pu JJ. PD-1 pathway and its clinical application: A 20 year journey after discovery of the complete human PD-1 gene. Gene. 2018;638:20-5. DOI: 10.1016/j.gene.2017.09.050
Khunger M, Hernandez AV, Pasupuleti V, Rakshit S, Pennell NA, Stevenson J, et al. Programmed cell death 1 (PD-1) ligand (PD-L1) expression in solid tumors as a predictive biomarker of benefit from PD-1/PD-L1 axis inhibitors: A systematic review and meta-analysis. JCO Precis Oncol. 2017;(1):1-15. DOI: 10.1200/PO.16.00030
Grizzi G, Caccese M, Gkountakos A, Carbognin L, Tortora G, Bria E, et al. Putative predictors of efficacy for immune checkpoint inhibitors in non-small-cell lung cancer: Facing the complexity of the immune system. Expert Rev Mol Diagn. 2017;17(12):1055- 69. DOI: 10.1080/14737159.2017.1393333
Hansen AR, Siu LL. PD-L1 testing in cancer: Challenges in companion diagnostic development. JAMA Oncol. 2016;2(1):15-6. DOI: 10.1001/jamaoncol.2015.4685
Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, et al. PD-L1 immunohistochemistry assays for lung cancer: Results from phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project. J Thorac Oncol. 2017;12(2):208‑22. DOI: 10.1016/j.jtho.2016.11.2228
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, et al. A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol. 2017;3(8):1051-8. DOI: 10.1001/jamaoncol.2017.0013
Büttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, et al. Programmed deathligand 1 immunohistochemistry testing: A review of analytical assays and clinical implementation in non- small-cell lung cancer. J Clin Oncol. 2017;35(34):3867‑76. DOI: 10.1200/JCO.2017.74.7642
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1– positive non–small-cell lung cancer. N Engl J Med. 2016;375(19):1823-33. DOI: 10.1056/NEJMoa1606774
Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD- L1-positive, advanced nonsmall-cell lung cancer (KEYNOTE-010): a randomised controlled trial. The Lancet. 2016;387(10027):1540-50. DOI: 10.1016/S0140-6736(15)01281-7
Powles T, Gschwend JE, Loriot Y, Bellmunt J, Geczi L, Vulsteke C, et al. Phase 3 KEYNOTE-361 trial: Pembrolizumab (pembro) with or without chemotherapy versus chemotherapy alone in advanced urothelial cancer. J Clin Oncol. 2017;35(15 suppl):TPS4590-TPS4590. DOI: 10.1200/JCO.2017.35.15_suppl.TPS4590
Galsky MD, Grande E, Davis ID, De Santis M, Arranz Arija JA, Kikuchi E, et al. IMvigor130: A randomized, phase III study evaluating first-line (1L) atezolizumab (atezo) as monotherapy and in combination with platinum-based chemotherapy (chemo) in patients (pts) with locally advanced or metastatic urothelial carcinoma (mUC). J Clin Oncol. 2018;36(15 suppl):TPS4589- TPS4589. DOI: 10.1200/JCO.2018.36.15_suppl.TPS4589
Silva MA, Ryall KA, Wilm C, Caldara J, Grote HJ, Patterson- Kane JC. PD-L1 immunostaining scoring for non-small cell lung cancer based on immunosurveillance parameters. Rosell R, editor. PLoS One. 2018;13(6):e0196464. DOI: 10.1371/journal.pone.0196464
Inoue Y, Yoshimura K, Mori K, Kurabe N, Kahyo T, Mori H, et al. Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung cancer. Oncotarget. 2016;7(22):32113-28. DOI: 10.18632/oncotarget.8528
Paré L, Pascual T, Seguí E, Teixidó C, González-Cao M, Galván P, et al. Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types. Ann Oncol. 2018;29(10):2121-8. DOI: 10.1093/annonc/mdy335
Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma. N Engl J Med. 2014;371(23):2189-99. DOI: 10.1056/NEJMoa1406498
Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, et al. First-line nivolumab in stage IV or recurrent non–small-cell lung cancer. N Engl J Med. 2017;376(25):2415-26. DOI: 10.1056/NEJMoa1613493
Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093-104. DOI: 10.1056/NEJMoa1801946
Ramalingam SS, Hellmann MD, Awad MM, Borghaei H, Gainor J, Brahmer J, et al. Abstract CT078: Tumor mutational burden (TMB) as a biomarker for clinical benefit from dual immune checkpoint blockade with nivolumab (nivo) + ipilimumab (ipi) in first-line (1L) non-small cell lung cancer (NSCLC): identification of TMB cutoff from CheckMate 568. Cancer Res. 2018;78(13 Suppl):CT078-CT078. DOI: 10.1158/1538-7445.AM2018-CT078
Ready N, Hellmann MD, Awad MM, Otterson GA, Gutierrez M, Gainor JF, et al. Firstline nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): Outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. J Clin Oncol. 2019; 37(12): 992-1000. DOI: 10.1200/JCO.18.01042
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 therapy 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
Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy. Science. 2018;362(6411):eaar3593. DOI: 10.1126/science.aar3593
Nadal E, Losa JH. Updates Biomarkers in Immuno-Oncology. ECO. 2018;1(1):1-13.
Chan TA, Yarchoan M, Jaffee E, Swanton C, Quezada SA, Stenzinger A, et al. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic. Ann Oncol. 2019;30(1):44-56. DOI: 10.1093/annonc/mdy495
Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51(2):202-6. DOI: 10.1038/s41588-018-0312-8
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-13. DOI: 10.1126/science.aan6733
Scarpa A, Cataldo I, Salvatore L. Microsatellite Instability - Defective DNA Mismatch Repair. OncologyPRO [Internet]. 2016 [accessed 03/13/2019]. Available at: https://oncologypro.esmo.org/Education-Library/Factsheets-on-Biomarkers/Microsatellite-Instability-Defective-DNA-Mismatch- Repair
Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen H- Z, et al. Landscape of Microsatellite Instability Across 39 Cancer Types. JCO Precis Oncol. 2017;(1):1‑15. DOI: 10.1200/PO.17.00073
Abida W, Cheng ML, Armenia J, Middha S, Autio KA, Vargas HA, et al. Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. JAMA Oncol. 2019;5(4):471-8. DOI: 10.1001/jamaoncol.2018.5801
Lemery S, Keegan P, Pazdur R. First FDA Approval Agnostic of Cancer Site — When a Biomarker Defines the Indication. N Engl J Med. 2017;377(15):1409-12. DOI: 10.1056/NEJMp1709968
Viale G, Trapani D, Curigliano G. Mismatch Repair Deficiency as a Predictive Biomarker for Immunotherapy Efficacy. BioMed Res Int. 2017;2017:1-7. DOI: 10.1155/2017/4719194
Schrock AB, Ouyang C, Sandhu J, Sokol E, Jin D, Ross JS, et al. Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer. Ann Oncol. 2019;30(7):1096-103. DOI: 10.1093/annonc/mdz134
Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, et al. IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127(8):2930-40. DOI: 10.1172/JCI91190
Solomon B, Young RJ, Rischin D. Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments. Semin Cancer Biol. 2018;52(Pt 2):228-40. DOI: 10.1016/j.semcancer.2018.01.008
Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al. Atezolizumab versus docetaxel for patients with previously treated nonsmall-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. The Lancet. 2016;387(10030):1837-46. DOI: 10.1016/S0140-6736(16)00587-0
DOI: http://dx.doi.org/10.7399%2Ffh.11328
Enlaces refback
- No hay ningún enlace refback.
Incluida en:
Farmacia Hospitalaria
Sociedad Española de Farmacia Hospitalaria. C/ Serrano n. 40 2º Dcha. - 28001 Madrid
eISSN: 2171-8695
ISSN-L: 1130-6343
Dep. Legal: M-39835-2012
Correo electrónico de contacto: [email protected]
Los artículos publicados en esta revista se distribuyen con la licencia: Creative Commons Attribution 4.0.
La revista Farmacia Hospitalaria no cobra tasas por el envío de trabajos, ni tampoco cuotas por la publicación de sus artículos.