LA REVOLUCIÓN DE LA INMUNOTERAPIA: INHIBIDORES DE PUNTOS DE CONTROL INMUNE PARA EL CÁNCER DE PULMÓN DE CÉLULAS NO PEQUEÑAS

  • Jordi Remon Centro Integral Oncológico Clara Campal (HM-CIOCC)
Palabras clave: cáncer de pulmón, inmunoterapia, linfocitos, punto de control inmunológico, biomarcador

Resumen

En los últimos años, el ámbito de la inmunoterapia contra el cáncer ha experimentado un progreso sobresaliente debido a la mejor comprensión sobre la biología de los linfocitos y su rápida traducción a ensayos clínicos. Los inhibidores de puntos de control inmunológico (ICI, por sus siglas en inglés) han demostrado un impacto significativo en el tratamiento de pacientes con cáncer de pulmón de células no pequeñas (CPCNP) surgiendo como una opción eficaz de tratamiento, incluso en el entorno de la primera línea. Los ICI pueden bloquear las vías inhibidoras que restringen la respuesta inmunitaria contra el cáncer, restaurando y manteniendo la inmunidad antitumoral. Actualmente hay 5 agentes disponibles para bloquear PD-1/PD-L1, y los regímenes que incluyen inmunoterapia sola o en combinación con quimioterapia u otro ICI, son ahora la opción preferida. Hay esfuerzos continuos para encontrar biomarcadores predictivos que permitan perfilar el patrón de respuesta a los ICIs. Las expresiones de PD-L1 cuantificada por inmunohistoquímica y la carga mutacional han emergido como los marcadores mejor validados en múltiples ensayos clínicos. Sin embargo, todavía existe la necesidad de mejorar la selección de los pacientes, y establecer cuáles de las terapias en son más efectivas en los diferentes entornos clínicos del CPCNP. Esta revisión presentará la utilidad de los ICIs en el CPCNP analizando los estudios clínicos más recientes, para discutir quienes tendrán el mayor beneficio para proporcionar una vía óptima que permita modificar los desenlaces de la enfermedad.

Biografía del autor/a

Jordi Remon, Centro Integral Oncológico Clara Campal (HM-CIOCC)
Departamento de Oncología Médica, Centro Integral Oncológico Clara Campal (HM-CIOCC), Hospital HM Delfos, HM Hospitales, Barcelona, España

Citas

1. Garon EB. Hellmann MD. Rizvi NA. Carcereny E. Leighl NB. Ahn MJ et al. Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Onccol, 2019;37(28):2518- 25234
2. Faivre-Finn C, Vicente D. Kurata T. Planchard D. PazAres L, Vansteenkiste J et al. LBA49 Durvalumab after chemoradiotherapy in stage III NSCLC: 4-year survival update from the phase III PACIFIC trial. Ann Oncol, 2020;31:S1178-S11781
3. Provencio M. Nadal E. Insa A. García-Campelo M. Casal-Rubio J. Dómine M et al. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label. Multicentre, single-arm. Phase 2 trial. Lancet Onco24, 2020;21(11):1413-14-8
4. Benitez JC. Remon J. Besse B. Current Panorama and Challenges for Neoadjuvant Cancer Immunotherapy. Clin Cancer Res, 2020;26(19):5068-50755
5. Teixido C. Reguart N, Using biomarkers to determine optimal combinations with immunotherapy (biomarker discovery perspective). Future OnEngl, 2020;16(23):1677- 1671
6. Tsao MS. Kerr KM. Kockx M. Beasley MB. Borczuk AC. Botling J et al. PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project. J Thorac Oncer, 2018;13(9):1302- 13113
7. Aguilar EJ. Ricciuti B. Gainor JF. Kehl KL. Kravets S. Dahlberg S et al. Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Ann Oncol, 2019;30(10):1653-1688.
8. Reck M. Rodríguez-Abreu D. Robinson AG. Hui R. Csőszi T. Fülöp A et al. Pembrolizumab vs. Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med, 2016;375(19):1823-1874
9. Brahmer JR. Rodriguez-Abreu D. Robinson AG. Hui R. Csőszi T. Fülöp A et al. KEYNOTE-024 5-year OS update: First-line (1L) pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) in patients (pts) with metastatic NSCLC and PD-L1 tumour proportion score (TPS) ≥50%. Ann Oncol, 2020;31:S1181-S11884
10. Mok TSK, Wu Y-L. Kudaba I. Kowalski D. Cho B, Turna H et al. Pembrolizumab vs. chemotherapy for previously untreated. PD-L1-expressing. Locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised. Open-label. Controlled. Phase 3 trial. LancEngl, 2019;393(10183):1819-183-7
11. Mok TSK, Wu Y-L. Kudaba I. Kowalski D. Cho B, Turna H et al. Final analysis of the phase III KEYNOTE-042 study: Pembrolizumab (Pembro) vs. platinum-based chemotherapy (Chemo) as first-line therapy for patients (Pts) with PD-L1–positive locally advanced/metastatic NSCLC. Ann Oncol, 2019;30:i363
12. Herbst RS. Giaccone G. De Marinis F. Reinmuth N, Vergnenegre A. Barrios CH et al. Atezolizumab for FirstLine Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med, 2020;383(14):1328-13346
13. Sezer A. Kilickap S. Gümüş M. Bondarenko I, Özgüroglu M. Gogishvili M et al. LBA52 EMPOWER-Lung 1: Phase III first-line (1L) cemiplimab monotherapy vs platinumdoublet chemotherapy (chemo) in advanced non-small cell lung cancer (NSCLC) with programmed cell deathligand 1 (PD-L1) ≥50%. Ann Oncol, 2020;31:S1182- S11885
14. Brahmer JR. Rodríguez-Abreu D. Robinson AG. Hui R. Csőszi T. Fülöp A et al. Health-related quality-of-life results for pembrolizumab vs. chemotherapy in advanced. PD-L1-positive NSCLC (KEYNOTE-024): a multicentre. International. Randomised. Open-label phase 3 trial. Lancet Oncol, 2017;18(12):1600-160-3
15. 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):2415-2493
16. Rizvi NA. Cho BC. Reinmuth N. Lee KH. Luft A. Ahn MJ et al. Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. JAMA Oncol, 2020;6(5):661-6737
17. Ramalingam SS. Ciuleanu TE. Pluzanski A. Lee J, Schenker M. Bernabe-Caro R et al. Nivolumab + ipilimumab vs. platinum-doublet chemotherapy as firstline treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1. J Clin Oncol, 2020;38(15_suppl):9500-9500
18. Hellmann MD. Paz-Ares L. Bernabe Caro R, Zurawski B. Kim S. Carcereny-Costa E et al. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med, 2019;381(21):2020-20331
19. Ready N. Hellmann MD. Awad MM. Otterson GA. Gutierrez M. Gainor JF et al. First-Line 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 Onccol, 2019;37(12):992-1042
20. Hellmann MD. Ciuleanu T-E. 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):2093-2146
21. Marabelle A. Fakih M. Lopez J, Shah M, Shapira-Frommer R. Nakagawa K et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort. Open-label. Phase 2 KEYNOTE-158 study. Lancet Oncol, 2020;21(10):1353-13-9
22. Ramalingam SS. Ciuleanu TE. Pluzanski A. Lee J, Schenker M. Bernabe-Caro R et al. Nivolumab + ipilimumab vs. platinum-doublet chemotherapy as firstline treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1. J Clin Oncol, 2020;38(15_suppl):9500-9500
23. Ferrara R. Facchinetti F. Calareso G. Kasraoui I, Signorelli D. Proto C et al. Hyperprogressive disease (HPD) upon first-line PD-1/PD-L1 inhibitors (ICI) as single agent or in combination with platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients (pts). Ann Oncol, 2020;31:S892
24. Gandhi L. Rodríguez-Abreu D. Gadgeel S. Esteban E. Felip E. De Angelis F et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med, 2018;378(22):2078-2005
25. Rodriguez-Abreu D. Powell SF. Hochmair M. Gadgeed SM. Esteban E. Felip E. Et al. Final analysis of KEYNOTE-189: Pemetrexed-platinum chemotherapy (chemo) with or without pembrolizumab (pembro) in patients (pts) with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). J Clin Oncol, 2020;38(15_suppl):9582-9582
26. Socinski MA. Jotte RM. Cappuzzo F. Orlandi F, Stroyakovskiy D. Nogasmi N et al. Atezolizumab for FirstLine Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med, 2018;378(24):2288-2348
27. Reck M. Mok TSK. Nishio M. Jotte R. Cappuzzo F. Orlandi F et al. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised. Open-label phase 3 trial. Lancet Respir Med, 2019;7(5):387-4-0
28. Papadimitrakopoulou V. Cobo M. Bordoni R. Bordoni R. Dubray-Longeras P Szalai Z et al. IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/ Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC. J Thorac Oncol, 2018;13(10):S332-S362
29. West H. McCleod M. Hussein M. Morabito A. Rittmeyer A. Conter HJ et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre. Randomised. Open-label. Phase 3 trial. Lancet Oncol, 2019;20(7):924-9-6
30. Yang Y, Wang Z. Fang J, Yu Q. Han B. Cang S et al. Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized. Double-Blind. Phase 3 Study (Oncology pRogram by InnovENT antiPD-1-11). J Thorac Oncer, 2020;15(10):1636-1614
31. Lu S, Yu Y, Yu X. Hu Y. Ma Z. Li X et al, Tislelizumab + chemotherapy vs chemotherapy alone as first-line treatment for locally advanced/metastatic nonsquamous NSCLC. Ann Oncol, 2020;31:S816-S877
32. Paz-Ares L. Luft A, Vicente D, Tafreshi A. Gümüs M. Mazières J et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med, 2018;379(21):2040-2065
33. Paz-Ares L, Vicente D, Tafreshi A. Robinson A, Soto Parra H. Mazières J et al. Pembrolizumab (pembro) + chemotherapy (chemo) in metastatic squamous NSCLC: Final analysis and progression after the next line of therapy (PFS2) in KEYNOTE-407. Ann Oncol, 2019;30:v918-v980
34. Jotte R. Cappuzzo F, Vynnychenko I, Stroyakovskiy D. Rodríguez-Abreu D. Hussein M et al. Atezolizumab in Combination With Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial. J Thorac Oncer, 2020;15(8):1351-1328
35. Wang J. Lu S. Hu C, Sun Y, Yang K. Chen M et al, Updated analysis of tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment of advanced squamous non-small cell lung cancer (SQ NSCLC). Ann Oncol, 2020;31:S878
36. Paz-Ares L. Ciuleanu TE, Yu X, Salman P. Pluzanski A. Nagrial A et al. Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (aNSCLC): CheckMate 227 - part 2 final analysis. Ann Oncol, 2019;30:xi67-xi04
37. Reck M. Ciuleanu T-E. Dols MC, Schenker M, Zurawski B. Menezes J et al. Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA. J Clin Oncol, 2020;38(15_suppl):9501-9501
38. Garassino M. Rodriguez-Abreu D. Gadgeel S. Esteban E. Felip E, Speranza G et al. Evaluation of TMB in KEYNOTE-189: Pembrolizumab Plus Chemotherapy vs Placebo Plus Chemotherapy for Nonsquamous NSCLC. J Thorac Oncol, 2019;14(10):S216-S227
39. Garassino MC. Gadgeel SM. Rodriguez-Abreu D. Felip E. Esteban E, Speranza G et al. Evaluation of blood TMB (bTMB) in KEYNOTE-189: Pembrolizumab (pembro) plus chemotherapy (chemo) with pemetrexed and platinum vs. placebo plus chemo as first-line therapy for metastatic nonsquamous NSCLC. J Clin Oncol, 2020;38(15_suppl):9521-9521
40. Socinski MA. Mok TS. Nishio M. Jotte RM. Cappuzzo F. Orlandi F et al. IMpower150 final analysis: Efficacy of atezolizumab (atezo) + bevacizumab (bev) and chemotherapy in first-line (1L) metastatic nonsquamous (nsq) nonsmall cell lung cancer (NSCLC) across key subgroups. Cancer Res, 2020;80(16 Supplement):CT216
41. Reck M. Mok T, Socinski MA. Jotte R. Lim D. Cappuzzo F et al. IMpower150: Updated efficacy analysis in patients with EGFR mutations. Ann Oncol, 2020;31:S837-S807
42. Mazieres J. Kowalski D. Luft A, Vicente D, Tafreshi A. Gümüs M et al. Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-SmallCell Lung Cancer. J Clin Onccol, 2020;38(3):271-248
43. Borghaei H. Langer CJ. Paz-Ares L. Rodríguez-Abreu D. Halmos B. Garassino MC et al. Pembrolizumab plus chemotherapy vs. chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PDL1 expression: A pooled analysis of 3 randomized controlled trials. Cancer, 2020;126(22):4867-4842
44. Waterhouse DM. Garon EB. Chandler J. McCleod M. Hussein M. Jotte R et al. Continuous Vs. 1-Year FixedDuration Nivolumab in Previously Treated Advanced Non-Small-Cell Lung Cancer: CheckMate 153. J Clin Onc10, 2020;38(33):3863-3831.
Publicado
2021-04-20
Sección
Artículos Especiales