Development of Immune-Related Adverse Events in Patients with Advanced NSCLC

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Immune checkpoint inhibitors (ICIs) have helped patients with non–small-cell lung cancer (NSCLC) achieve longer survival rates compared with traditional treatments.1 In patients with advanced NSCLC who have not been previously treated, the 3-year overall survival rate is 26.4%, and in previously treated patients, the rate is 19.0%.1 However, the use of ICIs is associated with immune-related adverse events (irAEs).1 A systematic review including ≥5000 patients with advanced NSCLC treated with ICIs alone found that 11% to 16% of patients experienced irAEs.1 When ICIs were combined with chemotherapy, 23% to 28% of patients experienced irAEs.1 Although these events require prompt recognition and clinical management, evidence shows that in patients with advanced solid tumors, the occurrence of irAEs may indicate better ICI efficacy.1 The development of skin rash or vitiligo in patients with melanoma was associated with better outcomes, but if the patient developed other irAEs, such as colitis, pneumonitis, or endocrinopathies, there was no survival advantage associated with irAEs.1 A similar association was seen to occur in patients with advanced NSCLC.1

In a retrospective study of 488 patients with advanced NSCLC who had been treated with single-agent ICIs in Italy between August 2013 and September 2021, the association of clinical and pathologic features with irAE development were analyzed.2 ICIs were used as first-line treatment in 35% of the patients and as a further line of treatment in 75% of patients. The median number of ICI treatment cycles was 6, with a range of 1 to 105 cycles. A total of 40.8% of patients experienced ≥1 irAEs; the most frequent irAEs were skin-related events and diarrhea (with a 20% rate for both conditions). In this study, irAEs caused 45% of patients to stop ICI treatment, and 18% permanently discontinued ICI treatment due to irAEs. Hospitalization occurred in 7.6% of patients, and 20% of patients developed ≥2 irAEs. For patients who experienced second irAEs, the rates of stopping or discontinuing ICI use or requiring hospitalization were similar. In patients who experienced ≥1 irAEs, an improved outcome was observed. Further analysis found that low tumor burden, defined as <2 involved organ sites, was an independent risk factor for development of irAEs. Patients who experienced skin-related irAEs had a median progression-free survival of 22.4 months and a median overall survival of 31.9 months versus patients with other irAEs (9.7 months and 18.5 months, respectively).2

The researchers concluded that “In real-world setting, the incidence of irAEs and their positive prognostic value were confirmed. Low tumor burden was associated with higher risk of irAEs. This could represent a starting point for the development of a nomogram capable to predict a global risk of irAEs and improve toxicity management.”2


  1. Remon J, Reguart N, Auclin E, Besse B. Immune-related adverse events and outcomes in patients with advanced non-small cell lung cancer: a predictive marker of efficacy? J Thorac Oncol. 2019;14(6):963-967.
  2. Pretelli G, Pavan A, Dal Maso A, et al. Immune-related adverse events (irAEs) in advanced non-small cell lung cancer (aNSCLC) patients (pts): a real-world analysis. Ann Oncol. 2022;33(2):S51.

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