Early mortality in patients with advanced non–small cell lung cancer (aNSCLC) and PD-L1 ≥ 50% receiving first-line immune checkpoint inhibitor (ICI): Analysis of the NOTCH collaborative REAL-SAIF study.

e20684 Background: Single-agent ICIs are approved for the first-line treatment of aNSCLC and PDL1 ≥50%. Early cross-over of survival curves raise concerns about early mortality in this group. Current controversies exist about upfront intensification with ICI-chemotherapy and the increasing use of ICIs in patients near the end-of-life. To our knowledge, this is one of the largest study to explore early mortality in patients with aNSCLC receiving single-agent ICI. Methods: 1571 patients treated between 2017-2023 from 18 UK centres were included into this retrospective real-world study. Multiple imputations were used to handle data missing at random and pooled estimates were combined. Multivariate logistic regression was used for 30- and 60-day mortality. Variables were selected through a combination of domain knowledge and LASSO regression. Results: 5.6% and 12.4% of patients experienced 30- and 60-day mortality respectively. Baseline demographics within total cohort were median age 70-years, 52% male, 76% non-squamous histology, 14% brain metastases, 11% liver metastases, 76% de-novo stage 4 disease, and 93% pembrolizumab as ICI of choice. Performance status (PS) of ≥2 (OR 2.36; p <0.001), neutrophil-lymphocyte ratio (NLR) (OR 1.21; p =0.008), neutrophil-eosinophil ratio (NER) (OR 1.33; p <0.001), and albumin (OR 0.88; p <0.001) were associated with 30-day mortality [Table 1]. PS ≥2 (OR 1.77; p <0.001), NLR (OR 1.39; p <0.001), NER (OR 1.29; p <0.001), albumin (OR 0.89; p <0.001), brain metastasis (OR 1.99; p =0.002), and liver metastasis (OR 1.88; p =0.007) were associated with 60-day mortality. Age, sex, BMI, smoking status, histology, and deprivation indices were not associated with 30- or 60-day mortality. Most common cause of 30-day death was NSCLC (79.6%) followed by non-cancer causes (11.4%). Conclusions: Poor PS and elevated inflammatory indices (NLR, NER, albumin) were associated with 30-day mortality, reflecting systemic effects of disease and/or patient frailty. The latter emergence of brain and liver metastases as 60-day prognostic markers may indicate the need for ICI-chemotherapy combination in fit patients. Multivariate logistic regression for 30-day and 60-day mortality. 30-day mortality[OR (95%CI); p -value] 60-day mortality[OR (95%CI); p -value] Age 0.98 (0.96-1.00) 0.086 1 (0.98-1.02) 0.907 Performance status ≥2 2.36 (1.63-3.42) <0.001 1.77 (1.31-2.39) <0.001 Haemoglobin 1.02 (1.00-1.03) 0.023 1.01 (1.00-1.02) 0.064 Albumin 0.88 (0.84-0.91) <0.001 0.89 (0.86-0.91) <0.001 NLR 1.21 (1.05-1.39) 0.008 1.39 (1.18-1.65) <0.001 NER 1.33 (1.14-1.54) <0.001 1.29 (1.12-1.48) <0.001 Brain metastasis – – 1.99 (1.29-3.06) 0.002 Liver metastasis – – 1.88 (1.19-2.98) 0.007 Index of Multiple Deprivation – – 1.06 (1.00-1.12) 0.062