Face to face among different chemo-immunotherapy combinations in the first line treatment of patients with advanced non-small cell lung cancer: Results of an international expert panel meeting by the italian association of thoracic oncology (AIOT).

Background: The combination of platinum-based chemotherapy with immune-checkpoint inhibitors (ICIs) is a standard of care option in the front-line treatment of advanced non-small cell lung cancer (NSCLC). Positive efficacy and safety results have been demonstrated with different chemo-ICI combinations in the corresponding clinical trials, however no randomized prospective comparison is available and there is no evidence on how to choose among the available regimens.

Methods: A virtual International Expert Panel took place in July 2023 to review data on chemo-ICI regimens available in the first-line setting in patients with NSCLC, and reach common considerations both in clinical practice and in research setting.

Results: Overall, all panelists agreed that safety of the chemo-immunotherapy combination regimens is supported by reviewed data, showing no additional toxicity concerns over those of the individual components of each regimen and highlighting differences in toxicity profile based on ICI component (single anti-PD-1 versus double anti-PD-1 and anti-CTLA-4). Among disease characteristics, PD-L1 value (<1%) but not histology was considered a potential selection factor in favor of the combination with dual ICI. With regards to clinical features, the panelists agreed that chemotherapy, whichever the ICI combination regimen, remains the backbone to counteract disease-related symptoms included those conditioning worse performance status. The panelists defined high, medium, and low priorities in clinical research. High priority was attributed to prospectively evaluating the impact of the addition of anti-CTLA-4 on brain metastasis, biomarker subgroups, and the optimal duration and schedule of combination regimens.

Conclusions: Based on the available evidence, the panelists reached common considerations on strengths and differences between chemotherapy plus single agent ICI and chemotherapy plus double agent ICIs in patients with advanced NSCLC. In the absence of direct comparison, different toxicity profile and subgroup analysis by PD-L1 are considered as the main potential features to select among the two regimens, however to be confirmed by recommended prospective randomized clinical research.