Early versus delayed initiation of first-line immune checkpoint inhibitors in metastatic non–small cell lung cancer: A real-world analysis of treatment timing and care context.

Abstract

e20660 Background: Immune checkpoint inhibitors (ICIs) are standard first-line therapy for metastatic non–small cell lung cancer (NSCLC) without targetable mutations. In real-world practice, the timing of ICI initiation varies and may reflect differences in clinical urgency and care pathways rather than treatment efficacy alone. We evaluated whether early versus delayed initiation of first-line ICIs is associated with survival and early healthcare utilization in metastatic NSCLC. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, including electronic health records from approximately 170 healthcare organizations. Adults (≥18 years) with stage IV NSCLC who received first-line immunotherapy (pembrolizumab, nivolumab, atezolizumab, durvalumab, or cemiplimab) were included. Patients were stratified by time from metastatic diagnosis to ICI initiation: early (≤30 days) versus delayed (30–90 days). Propensity score matching was performed for demographics and comorbidities. To minimize immortal time bias, overall survival (OS) was indexed to the date of stage IV diagnosis, while 90-day outcomes, including mortality, emergency department (ED) visits, hospitalizations, and intensive care unit (ICU) admissions, were indexed to the date of ICI initiation. Kaplan–Meier analyses and hazard ratios were used to compare outcomes. Results: After propensity score matching, 1,424 patients were included in each cohort. When overall survival was indexed to the date of metastatic diagnosis, there was no significant difference between patients initiating first-line ICIs within 30 days versus 30–90 days (median OS 732 vs 819 days; HR 1.05, 95% CI 0.95–1.16; log-rank p=0.351). Ninety-day mortality following ICI initiation was similar between groups (14.5% vs 13.0%; p=0.217), as were rates of ED or observation visits (30.2% vs 30.8%; p=0.714). However, earlier ICI initiation was associated with lower rates of acute hospitalization (40.2% vs 44.7%; p=0.015) but higher rates of ICU admission within 90 days of treatment initiation (41.1% vs 35.3%; p=0.002). Conclusions: In this real-world analysis of metastatic NSCLC restricted to first-line immunotherapy, initiation of ICIs within 30 days versus 30–90 days of diagnosis was not associated with differences in overall survival when survival was indexed to metastatic diagnosis. Earlier initiation was, however, associated with increased ICU utilization shortly after treatment initiation, suggesting greater clinical instability at the time therapy is started. In practice, awaiting sequencing results before starting immunotherapy is essential and thus the effect of time to initiation of immunotherapy needs further assessment via larger retrospective studies in an attempt to eliminate confounding variables.