4CPS-175 Effectiveness of immunotherapy as a function of age: meta-analysis of the approved combinations in first-line metastatic non-small-cell lung cancer in patients without mutations

Background and Importance It could be hypothesised that patients older than 65 years old may experience decreased immune function due to the natural aging process, which could lead to a more limited response to immunotherapy compared to those younger than 65 years old. The forest-plot analysis for age-dependent overall survival from the clinical trial of cemiplimab in combination with chemotherapy in locally advanced or metastatic non-small-cell lung cancer (NSCLC), EMPOWER-Lung 3, showed a borderline interaction between the subgroups younger and older than 65 years old, with a p-interaction=0.0895 (own calculation) and HR 0.53 (0.39–0.72), HR 0.81 (0.55–1.18), respectively. Aim and Objectives To verify the consistency of the hypothesis of an age-related effectiveness by a meta-analysis considering all approved immunotherapy combinations in first-line NSCLC. Material and Methods A MEDLINE-PubMed literature search was conducted for phase III randomised clinical trials (RCTs) with similar population and duration of pembrolizumab, atezolizumab ± bevacizumab, nivolumab + ipilimumab, durvalumab + tremelimumab and cemiplimab, in combination with chemotherapy and nivolumab + ipilimumab. A meta-analysis was performed with the MetaSurv calculator. The primary endpoint was overall survival (OS) in patients younger and older than, or equal to, 65 years of age. Age-dependent OS data for immunotherapy combinations versus a common comparator, platinum-based chemotherapy, were compared. Interaction was considered significative if p<0.05 and doubtful if 0.05≤p<0.1. Results A pooled HR of 0.67 (95% CI 0.58–0.76), p<0.000001 was obtained in patients younger than 65 years of age. Heterogeneity among trials estimate values were as follows: Q 14.84, p=0.03812. I2 53% (CI 95% 0–79%). In those older than 65 years old, the combined HR obtained was 0.77 (95% CI 0.70–0.84), p<0.000001. Heterogeneity estimate values were as follows: Q for heterogeneity 0.81 p=0.99733. I2 0% (CI 95% 0–0%). The calculated p-interaction between the combined HRs of the under-65 and over-65 groups was 0.0551, which is considered a doubtful interaction in a subgroup analysis. Conclusion and Relevance A significant benefit for immunotherapy-chemotherapy over chemotherapy alone was shown in both age groups. There is some consistency regarding a greater effectiveness of immunotherapy in patients under 65 years of age, but more data would be needed to confirm this possible difference. References and/or Acknowledgements Conflict of Interest No conflict of interest.