Current Immunotherapies for Lung Cancer: A Review for Respirologists
DOI:
https://doi.org/10.58931/cret.2025.112Abstract
Due to revolutionary advancements in treatment, lung cancer has had the largest improvement in mortality of all cancers over the last two decades. Despite this, it remains the type with the highest incidence and mortality of all cancers in Canada, and globally it has the second highest incidence and highest mortality.
An important mechanism for cancer cell survival, and one of the hallmarks of cancer, is evasion of destruction by immune cells. Immunotherapy is a class of systemic therapy aimed at activating the cytotoxic activity of immune cells and is one of the major drivers behind the improvement in survival of patients with lung cancer (along with targeted therapies, which will not be covered in this review). Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that disrupt immunosuppressive signaling and result in increased activity of cytotoxic T cells. This article discusses the currently available ICIs and their indications in the treatment of lung cancer, immune-related toxicities and important contraindications to treatment, and a respirology-focused overview of the management of toxicities. This is not a comprehensive review of immunotherapy trials in lung cancer.
References
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.
Canadian Cancer Statistics Advisory Committee in collaboration with the Canadian Cancer Society SC and the PHA of C. Canadian Cancer Statistics 2023 [Internet]. Canadian Cancer Statistics. Toronto, ON; 2023. Available from: cancer.ca/Canadian-Cancer-Statistics-2023-EN
Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12(1):31–46.
Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways similarities, differences, and implications of their inhibition. Am J Clin Oncol Cancer Clin Trials. 2016;39(1):98–106.
Udall M, Rizzo M, Kenny J, Doherty J, Dahm SA, Robbins P, et al. PD-L1 diagnostic tests: A systematic literature review of scoring algorithms and test-validation metrics. Diagn Pathol. 2018;13(1):1–11.
Sezer A, Kilickap S, Gümüş M, Bondarenko I, Özgüroğlu M, Gogishvili M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592–604.
Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, et al. Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC. N Engl J Med. 2020;383(14):1328–39.
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.
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(1):23–34.
Paz-Ares L, Ciuleanu TE, Cobo M, Schenker M, Zurawski B, Menezes J, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):198–211.
Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397(10272):375–86.
Burotto M, Zvirbule Z, Mochalova A, Runglodvatana Y, Herraez-Baranda L, Liu SN, et al. IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications. Ann Oncol [Internet]. 2023;34(8):693–702. Available from: https://doi.org/10.1016/j.annonc.2023.05.009
Garassino MC, Gadgeel S, Speranza G, Felip E, Esteban E, Hochmair MJ, et al. Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non–Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study. J Clin Oncol. 2023 Feb 21;41(11):1992–8.
Spain L, Diem S, Larkin J. Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev. 2016;44:51–60.
Abu-Sbeih H, Faleck DM, Ricciuti B, Mendelsohn RB, Naqash AR, Cohen J V., et al. Immune checkpoint inhibitor therapy in patients with preexisting inflammatory bowel disease. J Clin Oncol. 2020;38(6):576–83.
Atchley WT, Alvarez C, Saxena-Beem S, Schwartz TA, Ishizawar RC, Patel KP, et al. Immune Checkpoint Inhibitor-Related Pneumonitis in Lung Cancer: Real-World Incidence, Risk Factors, and Management Practices Across Six Health Care Centers in North Carolina. Chest. 2021;160(2):731–42.
Cho JY, Kim J, Lee JS, Kim YJ, Kim SH, Lee YJ, et al. Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer. Lung Cancer. 2018;125(September):150–6.
Rajan A, Sivapiromrat AK, McAdams MJ. Immunotherapy for Thymomas and Thymic Carcinomas: Current Status and Future Directions. Cancers (Basel). 2024;16(7).
National Cancer Institute, National Institutes of Health UD of H and HS. Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. [Internet]. [cited 2024 Sep 30]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf
Schneider BJ, Naidoo J, Santomasso BD, Lacchetti C, Adkins S, Anadkat M, et al. Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol. 2021;39(36):4073–126.
Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab, with or without tremelimumab, plus platinum–etoposide versus platinum–etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):51–65.
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):1301–11.
