Immune Checkpoint Inhibitors in Early-Stage Non-Small Cell Lung Cancer: New standard of Care?
Journal: Advances in Medicine and Engineering Interdisciplinary Research DOI: 10.32629/ameir.v2i3.2458
Abstract
Worldwide, lung cancer is the first cancer in incidence and mortality. The most common histological type is non-small cell lung cancer (NSCLC). At an early stage, resection is the standard curative treatment, but relapse is high, which could be explained by micrometastatic disease. Adjuvant and neoadjuvant chemotherapy have little benefits in disease-free survival and overall survival, which is why new strategies have been studied. Immune checkpoint inhibitors (ICI) act by increasing the surveillance of the immune system. They have been used for years in advanced stage NSCLC, however, new schemes in earlier stages, be it as adjuvant therapy, neoadjuvant therapy or both, have demonstrated an important benefit in the endpoints studied. This review aims to describe the biologic rationale of ICIs in early-stage NSCLC and discuss the selected trials and endpoints.
Keywords
non-small cell lung cancer (NSCLC); immunotherapy; immune checkpoint inhibitor
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[2] Burotto M, Aren O, Renner A, Samtani S, Jimenez de la Jara J. Lung cancer in Chile. J Thorac Oncol. 2019;14(9):1504-1509. Disponible en: doi:10.1016/j.jtho.2019.02.024
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[8] Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res. 2014;3(4):242-249. Disponible en: doi: 10.3978/j.issn.2218-6751.2013.12.05
[9] Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, et al.; LACE Collaborative Group. Lung adjuvant cisplatine valuation: a pooled analysis by the LACE Collaborative Group. J ClinOncol. 2008;26(21):3552-3559. Disponible en: doi: 10.1200/JCO.2007.13.9030
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[11] Gilligan D, Nicolson M, Smith I, Groen H, Dalesio O, et al. Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet. 2007;369(9577):1929-1937. Disponible en: doi: 10.1016/S0140-6736(07)60714-4
[12] Dautzenberg B, Benichou J, Allard P, Lebeau B, Coetmeur D, Brechot JM, et al. Failure of the perioperative PCV neoadjuvant polychemotherapy in resectable bronchogenic non-small cell carcinoma. Results from a randomized phase II trial. Cancer. 1990;65(11):2435-2441. Disponible en: doi:10.1002/1097-0142(19900601)65:11<2435::aidcncr2820651105>3.0.co;2-213.
[13] Mamdani H, Matosevic S, Khalid AB, Durm G, Jalal SI. Immunotherapy in lung cancer: current landscape and future directions. Front Immunol. 2022;13:823618. Disponible en: doi: 10.3389/fimmu.2022.82361814
[14] Lahiri A, Maji A, Potdar PD, Singh N, Parikh P, Bisht B, et al. Lung cancer immunotherapy: progress, pitfalls, and promises. Mol Cancer. 2023;22(1):40. Disponible en: doi: 10.1186/s12943-023-01740-y
[15] Luo W, Wang Z, Zhang T, Yang L, Xian J, Li Y, et al. Immunotherapy in non-small cell lung cancer: rationale, recent advances and future perspectives. Precis Clin Med. 2021;4(4):258-270. Disponible en: doi: 10.1093/pcmedi/pbab027
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[19] Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, vonPawel J, et al.; OAK Study Group. Atezolizumab vs docetaxel inpatients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255-265. Disponible en: doi: 10.1016/S0140-6736(16)32517-X Erratum in: Lancet. 2017;389(10077):e5.
[20] Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al.; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078-2092. Disponible en: doi: 10.1056/NEJMoa1801005
[21] Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, et al. Five-year survival outcomes from the pacific trial: durvalumab after chemoradiotherapy in stage iii non-small-cell lung cancer. J Clin Oncol. 2022;40(12):1301-1311. Disponible en: doi: 10.1200/JCO.21.01308.
[22] Felip E, Altorki N, Zhou C, Csƅszi T, Vynnychenko I, Goloborodko O, et al.; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-1357. Disponible en: doi: 10.1016/S0140-6736(21)02098-5
[23] Felip E, Altorki N, Zhou C, Vallières E, Martínez-Martí A, Rittmeyer A, etal. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023;34(10):907-919. Disponible en: doi: 10.1016/j.annonc.2023.07.001
[24] O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, et al.; EORTC-1416-LCG/ETOP 8-15 - PEARLS/KEYNOTE-091 Investigators. Pembrolizumab vs placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022;23(10):1274-1286. Disponible en: doi: 10.1016/S1470-2045(22)00518-6
[25] Oselin K, Shim BY, Okada M, Bryl M, Bonanno L, Demirag G, et al. Pembrolizumab vs placebo for early-stage non-small-cell lung cancer after resection and adjuvant therapy: subgroup analysis of patients who received adjuvant chemotherapy in the phase 3 PEARLS/KEYNOTE-091 study. J Clin Oncol. 2023;41(16_suppl):8520-8520. Disponible en: doi: 10.1200/JCO.2023.41.16_suppl.8520
[26] Sorscher S. Pembrolizumab as adjuvant therapy in non-small-cell lung cancer. Lancet Oncol. 2022;23(12):e529. Disponible en: doi: 10.1016/S1470-2045(22)00682-9
[27] Uprety D. Pembrolizumab as adjuvant therapy in non-small-cell lung cancer. Lancet Oncol. 2022;23(12):e527. Disponible en: doi: 10.1016/S1470-2045(22)00636-2
[28] Liu J, Blake SJ, Yong MC, Harjunpää H, Ngiow SF, Takeda K, et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. Cancer Discov. 2016;6(12):1382-1399. Disponible en: doi: 10.1158/2159-8290.CD-16-0577
[29] Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM,et al.; CheckMate 816 Investigators. Neoadjuvant nivolumabplus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973-1985. Disponible en: doi: 10.1056/NEJMoa2202170
[30] Provencio M, Nadal E, González-Larriba JL, Martínez-Martí A, Bernabé R, Bosch-Barrera J, et al. Perioperative nivolumab and chemotherapy in stage iii non-small-cell lung cancer. N Engl J Med. 2023;389(6):504-513. Disponible en: doi: 10.1056/NEJMoa2215530
[31] Provencio M, Serna R, Nadal E, Larriba JLG, Martínez-Martí A, Bernabé R, et al. PL03.12 Progression free survival and overall survival in NADIM ii study. J Thorac Oncol. 2022;17(9):S2-S3. Disponible en: doi: 10.1016/j.jtho.2022.07.014
[32] Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, et al.; KEYNOTE-671 Investigators. Perioperative pembrolizumab for early stage non-small-cell lung cancer. N Engl J Med. 2023;389(6):491-503. Disponible en: doi: 10.1056/NEJMoa2302983
[33] Wakelee HA, Liberman M, Kato T, Tsuboi M, Lee SH, He J, et al. KEYNOTE-671: randomized, double-blind, phase 3 study of pembrolizumab or placebo plus platinum based chemotherapy followed by resection and pembrolizumab or placebo for early stage NSCLC. J Clin Oncol. 2023;41(17_suppl):LBA100-LBA100. Disponible en: doi:10.1200/JCO.2023.41.17_suppl.LBA100
[34] Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, et al.; AEGEAN Investigators. Perioperative durvalumab for resectable non-small-cell lung cancer. N Engl J Med. 2023;389(18):1672-1684. Disponible en: doi: 10.1056/NEJMoa2304875
[35] Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, et al. LBA1 CheckMate 77T: Phase III study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage II–IIIb NSCLC. Ann Oncol. 2023;34:S1295. Disponible en: doi: 10.1016/j.annonc.2023.10.050
[36] Lu S, Wu L, Zhang W, Zhang P, Wang W, Fang W, et al. Perioperative toripalimab +platinum doublet chemotherapy vs chemotherapy in resectable stage II/III non-small cell lung cancer (NSCLC): Interimevent-free survival (EFS) analysis of the phase III Neotorch study. J Clin Oncol. 2023;41(36_suppl):425126-425126. Disponible en: doi: 10.1200/JCO.2023.41.36_suppl.425126
[37] Cordeiro de Lima VC, Corassa M, Saldanha E, Freitas H, Arrieta O, RaezL, et al. STK11 and KEAP1 mutations in non-small cell lung cancer patients: descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP). Lung Cancer. 2022;170:114-121. Disponible en: doi:10.1016/j.lungcan.2022.06.010
[38] West HJ, McCleland M, Cappuzzo F, Reck M, Mok TS, Jotte RM, et al. Clinical efficacy of atezolizumab plus bevacizumab and chemotherapy in KRAS-mutated non-small cell lung cancer with STK11, KEAP1, or TP53 comutations: subgroup results from the phase III IMpower150 trial. J Immunother Cancer. 2022;10(2):e003027. Disponible en: doi: 10.1136/jitc-2021-003027
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