Abstract 415P
Background
With nearly one-third of patients with advanced NSCLC and PD-L1 TPS ≥50% surviving beyond five years following first-line pembrolizumab, long-term outcomes challenge traditional paradigms of cancer prognostication. The emergence of non-cancer-related factors and time-dependent trends underscore the need for advanced analytical frameworks to unravel their complex interplay.
Methods
We analyzed the Pembro-real 5Y registry, a global real-world dataset of 1,050 patients treated across 61 institutions in 14 countries with a long-term follow-up and a large panel of baseline variables. Two complementary approaches were employed: ridge regression, chosen for its ability to address multicollinearity while retaining interpretability, and NAIM, a transformer-based AI model designed to handle missing data without imputation. Endpoints included risk of death at 6, 12, 24, 60 months and 5-year survival.
Results
The ridge regression model achieved a c-statistic of 0.66 (95% CI: 0.59–0.72) for the risk of death and an AUC of 0.72 (95%CI: 0.65–0.78) for 5-year survival, identifying ECOG-PS ≥2, increasing age, and metastatic burden as primary risk factors. However, wide confidence intervals for some predictors highlighted statistical instability. NAIM demonstrated robust handling of missing data, with a c-index of 62.98 ± 2.11 for risk of death and an AUC of 60.52 ± 3.71 for 5-year survival. The comprehensive SHAP analysis revealed dynamic, time-dependent patterns, with early mortality dominated by acute factors (e.g., ECOG-PS, steroids) and long-term outcomes increasingly influenced by systemic health (e.g., absence of hypertension/CV comorbidities, BMI). Unexpected insights included the protective role of dyslipidemia (but not statins) and the nuanced impact of smoking status, reflecting evolving disease dynamics and host-tumor interplay.
Conclusions
Our integrative framework illuminates the complexity of long-term outcomes in patients with NSCLC uncovering dynamic, nonlinear prognostication trends. This analysis provides insights into patient trajectories, emphasizing the need for holistic, long-term management strategies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Cortellini: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD; Financial Interests, Personal, Advisory Board: Regeneron, Roche, BMS, Amgen, Daiichi Sankyo. R. Giusti: Financial Interests, Personal, Invited Speaker, Writing Engagement: Roche; Financial Interests, Personal, Other, Travel Grant: Pfizer; Financial Interests, Personal, Other, Travel Grant Advisory Board: Takeda. M. Tiseo: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Roche, Amgen, Takeda, MSD, Merck, BMS, Pfizer, Eli Lilly, Novartis, Janssen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Roche. All other authors have declared no conflicts of interest.