Immunotherapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer - Challenges and Perspectives

Sep 23, 2026

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Lung cancer is a major cause of cancer mortality, disproportionately affecting elderly patients who often have comorbidities and reduced organ function. Immune checkpoint inhibitors (ICIs) may be better tolerated than chemotherapy, yet their efficacy and safety in elderly non-small cell lung cancer (NSCLC) populations remain insufficiently characterized due to limited trial inclusion. This narrative review evaluates evidence in patients aged 65+ treated with ICIs, assessing overall survival, progression-free survival, response rates, treatment-related adverse events, and the role of immunosenescence. Overall, evidence supports benefit and safety in fit older adults, while immunosenescence and limited data in the very elderly constrain generalizability.

LanguageEnglish

CategoryHealthcare

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Pages17

Reading Time43 min

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Introduction

Epidemiology and burden in older adults

Age-related differences in immunotherapy responses

Abstract

Keywords

Review Immunotherapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer: Challenges and Perspectives Anass Baladi 1, *, Hassan Abdelilah Tafenzi 1,2, Othmane Zouiten 1, Leila Afani 1, Ismail Essaadi 2,3, Mohammed El Fadli 1 and Rhizlane Belbaraka 1,2 Academic Editors: Ilaria Marrocco and Donatella Romaniello Received: 7 January 2025 Revised: 30 January 2025 Accepted: 30 January 2025 Published: 27 February 2025 Citation: Baladi, A.; Tafenzi, H.A.; Zouiten, O.; Afani, L.; Essaadi, I.; El Fadli, M.; Belbaraka, R. Immunotherapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer: Challenges and Perspectives. Int. J. Mol. Sci. 2025, 26, 2120. [https://](https://)[ ](https://)[doi.org/10.3390/ijms26052120](doi.org/10.3390/ijms26052120) [Copyright:](Copyright:) © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Department of Medical Oncology, Mohammed VI University Hospital, Marrakech 40000, Morocco; [hassanabdelilah.tafenzi@gmail.com](hassanabdelilah.tafenzi@gmail.com) (H.A.T.); [drzouitenothmane@gmail.com](drzouitenothmane@gmail.com) (O.Z.); [afanileila@gmail.com](afanileila@gmail.com) (L.A.); [elfadli.mohamed2000@gmail.com](elfadli.mohamed2000@gmail.com) (M.E.F.); [belbaraka.r@gmail.com](belbaraka.r@gmail.com) (R.B.) 2 Laboratory of Biosciences and Health, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech 40000, Morocco; [ismail_onco@yahoo.fr](ismail_onco@yahoo.fr) 3 Medical Oncology Department, Avicenna Military Hospital, Marrakech 40000, Morocco * Correspondence: [anassbaladi2020@gmail.com](anassbaladi2020@gmail.com) Abstract: Lung cancer, a leading cause of cancer-related mortality, disproportionately affects the elderly, who face unique challenges due to comorbidities and reduced organ function. Immune checkpoint inhibitors (ICIs) offer a more tolerable alternative to chemotherapy, but their efficacy and safety in elderly non-small cell lung cancer (NSCLC) patients remain underexplored due to limited representation in clinical trials. A narrative literature review was conducted using PubMed, Embase, and the Cochrane Library to evaluate studies on elderly NSCLC patients (≥65 years) treated with ICIs. Key outcomes assessed included overall survival, progression-free survival, response rates, treatment-related adverse events, and the influence of immunosenescence on treatment efficacy. The review highlighted evidence supporting the efficacy and safety of ICIs in elderly NSCLC patients, particularly those with good performance status. Age-related immunosenescence may affect outcomes, emphasizing the need for individualized treatment. Limited data suggest ICIs alone maybe preferable to chemo-immunotherapy for patients over 75 years. However, the exclusion of elderly patients from clinical trials and methodological limitations reduces the generalizability of these findings. ICIs hold promise for advanced NSCLC in older adults, but tailored approaches and greater elderly inclusion in trials are needed to optimize outcomes. Keywords: lung cancer; elderly patients; immune checkpoint inhibitors; non-small cell lung cancer; immunosenescence 1. Introduction Lung cancer is a significant health concern worldwide. In 2020 alone, nearly 1.8 million deaths were reported out of 2.2 million newly diagnosed cases [1,2] . The agestandardized incidence rate of lung cancer, which measures the number of new cases per 100,000 individuals each year, shows considerable variation across different countries. For instance, Denmark reports a rate of 36.8 per 100,000, while Mexico has a considerably lower rate of 5.9 per 100,000 [3,4] . This disease is a significant concern in developing countries like China, wh

FAQs

Why are elderly patients with advanced NSCLC considered a special population for immunotherapy?

They are more likely to have comorbidities and reduced organ function, which can limit tolerability of chemotherapy and complicate treatment decisions. The review emphasizes that age-related factors influence outcomes and safety.

What does the review use to assess the effectiveness of ICIs in elderly NSCLC patients?

It evaluates studies in elderly NSCLC patients (≥65 years) using outcomes including overall survival, progression-free survival, response rates, and treatment-related adverse events. It also considers immunosenescence as a potential modifier of benefit.

What key evidence does the review highlight about ICIs in elderly patients?

Evidence supports efficacy and safety of ICIs in elderly NSCLC patients, particularly those with good performance status. The review also notes limited data suggesting potential preference for ICI monotherapy over chemo-immunotherapy for patients over 75.

Sep 23, 2026

Uploaded by Miles