The significance of MDM-2 positivity in stage 4 non-small cell lung cancer.

e20599 Background: MDM-2 positivity is discussed as a potential indicator of resistance to immunotherapy and targeted therapies in many cancer types. Our study will investigate the effect of MDM-2 levels on treatment response and overall survival in patients with unresectable/metastatic NSCLC, the majority of whom received second-line or later immunotherapy(IO). Methods: 81 patients followed at our center were included in the study. Immunohistochemical evaluation of MDM-2 levels was performed on the pathology slides of our patients. The distribution of best response after IO was recorded as follows: CR 11 (16.2%), PR 41 (60.3%), PD 11 (16.2%), and mixed response 5 (7.4%). Statistically significant differences were found in the following variables: bone metastasis, liver metastasis, duration of IO, best response after IO, hemoglobin level, and progression status. Bone metastasis (p = 0.001) and liver metastasis ( p = 0.037) were more frequent in patients who died. The duration of IO was longer in the surviving group, with a median of 16.5 months (IQR: 6.0–31.5), compared to a median of 3.0 months (IQR: 2.5–8.5) in the death group (p < 0.001). Hb levels were higher in the surviving group (median 12.80) and lower in the death group (median 11.5) (p = 0.003). The distribution of best response after IO differed significantly between the two groups (p < 0.001); the complete response rate was higher in the surviving group (Survivors: 32.3%; Deaths: 2.7%). Results: The survival difference between the two groups, categorized as MDM-2 levels ≤2 and > 2, was statistically significant. Median survival was 26.3 months in the MDM-2 ≤2 group and 6.6 months in the MDM-2 > 2 group . In the MDM-2 ≤2 group, survival rates were found to be 69.9% (SE = 6.1) at 1 year, 46.0% at 3 years, 28.6% (SE = 8.6) at 5 years, and 14.3% at 10 years; in the MDM-2 > 2 group, the survival rate was determined to be 52.9% (SE = 11.4) at 1 year and 16.5% at 3 years.(p = 0,033). Conclusions: We believe that our study will make a significant contribution to the literature as it is the first real-life study investigating IO resistance in unresectable/metastatic NSCLC, showing a significant association between MDM-2 levels and survival. MDM-2 % <2 >2 Survival Rate % SE % SE 1 year 69,9 6,1 52,9 11,4 3 years 46,0 6,9 16,5 10,1 5 years 28,6 8,6 10 years 14,3 11,0