Real-world incidence of pneumonitis in different treatment modalities of advanced non-small cell lung carcinoma

Cuperus, J.H.; Kalkhoran, H.A.; Codrington, H.; Visser, L.E. (2025)

Article / Letter to editor

Background: The treatment landscape for non-small cell lung cancer (NSCLC) has evolved with the introduction of immunotherapy, targeted therapy, and combinations with chemotherapy. However, therapy-related pneumonitis (TRP) poses a significant challenge, often leading to treatment discontinuation and respiratory failure. The incidence of TRP is frequently underestimated in clinical trials, and its associated risk factors remain underexplored. This study aimed to investigate the real-world incidence and risk factors for TRP across various NSCLC treatment regimens.

Methods: This retrospective cohort study included patients diagnosed with stage III or IV NSCLC and who started at least one of the 11 predefined systemic anti-cancer treatment regimens (comprising chemotherapy, immunotherapy, or targeted therapy) at Haga Teaching Hospital between January 2016 and January 2024. Clinical data were extracted from Electronic Health Records using text-mining based software. The objective was to determine the incidence rate (IR) per 100 person-years (PY) of grade >= 2 TRP requiring systemic corticosteroids across the treatment regimens. Risk factors for TRP were analyzed using Cox proportional hazards models.

Results: A total of 801 treatment regimens were followed on TRP in our cohort of 636 patients. The IRs varied across regimens, with the highest IR observed in patients receiving durvalumab following chemoradiotherapy (CRT) (27.7 per 100 PY). Among CRT regimens, the IR was higher in patients treated with etoposide compared to those receiving pemetrexed (20.5 vs. 8.5 per 100 PY). Pembrolizumab monotherapy exhibited a lower IR compared to its combination with platinum/paclitaxel or platinum/pemetrexed (6.6 vs. 16.6 and 8.9 per 100 PY, respectively). Certain chemotherapy and targeted therapy regimens reported no cases of TRP during the study period. Furthermore, the real-world incidence of TRP was higher than reported in pivotal clinical trials. Identified risk factors for TRP included higher body mass index and radiation fractions.

Conclusion: As NSCLC treatment evolves, addressing TRP risks becomes pivotal for ensuring the best possible patient outcomes. This large-scale real-world study provides valuable insights into the association between NSCLC treatment regimens and TRP, as well as the risk factors of TRP.

• Non-small-cell lung carcinoma
• Therapy-related pneumonitis
• Immune checkpoint inhibitors
• Chemotherapy
• Chemoradiotherapy
• Tyrosine kinase inhibitor
• Real-world data
• Incidence
• Risk factors

• All authors: Cuperus, J.H.; Kalkhoran, H.A.; Codrington, H.; Visser, L.E.
• Date: 2025-10-25
• Journal: Lung Cancer
• Volume: 209
• DOI: doi:10.1016/j.lungcan.2025.108744