Hello, everyone. I would like to thank the scientific committee for the opportunity to present our work reporting on the comparative outcomes of pembrolizumab and the combination of pembrolizumab with platinum-based chemotherapy in correlation with blood-based biomarkers in treatment with AFP-DL1 high-advanced non-small cell lung cancer. This is my financial disclosure. Both pembrolizumab and the combination of pembrolizumab with platinum-based chemotherapy represent start-on fast-line options for advanced non-small cell lung cancer with PD-L1 tumor proportion score greater than 50%. Non-predictive biomarkers exist to guide treatment decisions. In our study, 423 consecutive patients with advanced non-small cell lung cancer were identified in electronic databases of high-risk lung cancer centers. Overall survival was assessed in each of the treatment groups in correlation with the selected blood-based biomarkers using the cut-offs established earlier. Finally, a predictive DNLR-based score was developed in order to predict which patients will derive the benefits from adding chemotherapy. Baseline characteristics were well-balanced between the groups, except for age and ECOG performance status differences in favor of the combined therapy group. The distribution of blood-based biomarkers was homogenous in the two groups. A propensity score matching analysis was performed and patients were matched for age, sex, and ECOG performance status. In the entire cohort, better overall survival with the combined treatment was initially observed, which was attributed to the imbalances in baseline characteristics in favor of the combined modality group. Indeed, after controlling the imbalances in the matched cohort, no overall survival benefit for adding chemotherapy to pembolizumab has been seen. In the univariate analysis of factors affecting overall survival in patients treated with pembolizumab, all the blood biomarkers, except for SII, along with age and ECOG performance status demonstrated a significant correlation. Multivariate overall survival analysis was performed separately for each of the selected biomarkers and included age, sex, ECOG performance status, histological subtype, as well as the biomarker of interest. All the biomarkers remained associated with overall survival in a statistically significant manner. In the univariate analysis in patients treated with the combined therapy, none of the biomarkers demonstrated a significant correlation. We next evaluated the univariate Cox proportional hazard regression model incorporating selected clinical factors on all the listed biomarkers and assessing their overall survival impact in correlation with the treatment type in the entire cohort. Furthermore, favorable overall survival with the combined treatment was observed in patients older than 65 years old, females, never smokers, patients with adenopasmal mystology, NLR, DNLR, and ELR-graded endocytes, highly lowered endocytes, and Lipi 1 or 2. We attempted to develop a score that will be able to predict which patients will derive an overall survival benefit from the combined therapy. In the proposed predictive score, we incorporated parameters that have been shown to predict different outcomes, choosing the blood-based biomarker to be included in the proposed predictive score. We looked for the biomarker with a prominent ability to predict outcomes and the biomarker representing most patients in the entire cohort. Guided by these principles, we chose DNLR to be incorporated in the predictive score. Thus, the predictive score grading from 0 to 5 including the following parameters. Patients with scores 3 to 5 treatment with the combined therapy had significantly longer overall survival as compared to patients with pembrolizumab alone. On the contrary, in patients with score 0 to 2, overall survival was not statistically different between the two groups. In conclusion, both pembrolizumab and the combined therapy seem to be associated with similar long-term outcomes. However, the treatment effects differ in various patient subsets. Treatment decisions should be individualized and considered based on patients' clinical and laboratory characteristics. The suggested predictive DNLR-based score may help in guiding treatment decisions. However, a prospective validation is required. I would like to thank all my collaborators and thank you for your attention.

pembrolizumab

chemotherapy

advanced non-small cell lung cancer

blood-based biomarkers

overall survival