Cutaneous immune-related adverse events associated with improved progression-free survival in non-small cell lung cancer

This meta-analysis reviewed data from studies involving patients with non-small cell lung cancer treated with anti-PD-1, PD-L1, or chemotherapy. The analysis included a total sample size of 4259 patients. The setting of the included studies was not reported. The primary focus was on the association between cutaneous immune-related adverse events and survival outcomes. The comparator groups included patients with no irAEs, patients with any irAEs, and comparisons between ICI monotherapy versus chemo-immunotherapy or mixed cohorts. The follow-up period for the aggregated data was 1.4 months.

The primary outcomes assessed were overall survival and progression-free survival. The development of cutaneous immune-related adverse events was associated with improved progression-free survival. The hazard ratio for this association was 0.40 with a 95% confidence interval of 0.33-0.50. Similarly, the development of these events was associated with improved overall survival. The hazard ratio for overall survival was 0.43 with a 95% confidence interval of 0.35-0.53. Absolute numbers for these outcomes were not reported in the source data.

When comparing patients with cutaneous immune-related adverse events to those with any irAEs, the progression-free survival was longer in the cutaneous group. The hazard ratio for this comparison was 0.70 with a 95% confidence interval of 0.55-0.89. In the subgroup of patients receiving ICI monotherapy, cutaneous immune-related adverse events were associated with improved overall survival. The hazard ratio was 0.45 with a 95% confidence interval of 0.35-0.58. Progression-free survival in this monotherapy subgroup also showed improvement with a hazard ratio of 0.54 and a 95% confidence interval of 0.44-0.65.

In contrast, no survival advantage was observed for patients receiving chemo-immunotherapy or in mixed cohorts. For overall survival in these groups, the hazard ratio was 1.08 with a 95% confidence interval of 0.69-1.70. For progression-free survival in these same cohorts, the hazard ratio was 0.99 with a 95% confidence interval of 0.62-1.56. Safety data, including adverse events, serious adverse events, discontinuations, and tolerability, were not reported. The study did not provide absolute numbers for adverse events.

Key methodological limitations include immortal time bias inherent in aggregate data and treatment heterogeneity across the included studies. Funding or conflicts of interest were not reported. The certainty of the evidence was not reported. These limitations prevent definitive causal conclusions regarding the skin reactions and survival outcomes. The association observed may reflect underlying patient biology rather than a direct effect of the adverse event itself.

Clinically, cutaneous immune-related adverse events provide refined prognostic discrimination compared with any irAEs. This supports their utility as a distinct biomarker to guide treatment decisions. However, clinicians must interpret these findings cautiously given the observational nature of the data. The lack of safety reporting limits the ability to weigh risks against benefits. Further research is needed to clarify the relationship between skin reactions and treatment efficacy in different therapeutic contexts.