Disease kinetics and practice patterns in ≥ 4-year long-term beneficiaries of immune checkpoint inhibitors for advanced non–small cell lung cancer.

8561 Background: Immune checkpoint inhibitors (ICIs) have transformed outcomes in advanced non-small cell lung cancer (NSCLC), enabling durable responses in a subset of patients (pts). However, detailed clinical trajectories and patterns of late disease progression among long-term survivors remain poorly characterized. Methods: This multicenter retrospective cohort study enrolled advanced NSCLC pts who initiated ICI-containing therapy between January 2015 and April 2020. Long-term beneficiaries (LTBs) were defined as pts achieving both overall survival (OS) and time to next cytotoxic chemotherapy (TTNC) ≥4 years (yrs). We performed 4-yr landmark analyses, characterized late progression (defined as the first radiographic progression ≥4 yrs from ICI initiation), and evaluated cause-specific mortality using competing risk analysis. Results: Of 3,144 pts, 537 (17%) survived ≥4 yrs; 295 (9.4%) were LTBs (median follow-up, 68.6 months; only 8.1% lost to follow-up). ICI was initiated as first-line therapy in 186 pts (63.1%) and as second-line or later in 109 pts (36.9%). The median age was 67 yrs, and PD-L1 Tumor Proportion Score ≥50% was observed in 57%. Among 235 LTBs without progression at 4 yrs, 156 (66%) had discontinued ICI. Among pts progression-free at 4 yrs, lung cancer-specific OS (LC-OS) rates from ICI initiation were 97.8% at 6 yrs and 88.0% at 8 yrs (Table). Late progression occurred in 26 of 235 progression-free LTBs (11.1%); all had progression involving ≤5 lesions. The median interval from the last non-progressive assessment to the first assessment meeting radiographic progression was 98 days (IQR, 56–189), with a median sum-of-diameters growth rate of 6.2 mm/month (IQR, 3.4–9.6). Local therapy was selected in 42% after progression. Among 22 deaths occurring ≥4 yrs after ICI initiation, only 7 (32%) were lung cancer–related, whereas 15 (68%) were due to other causes, including five secondary malignancies. Competing risk analysis showed that the cumulative incidence of other-cause death consistently exceeded that of lung cancer death throughout follow-up (lung cancer death: 0.5% at 5 yrs to 10.7% at 8 yrs; other-cause death: 2.3% to 14.8%). Conclusions: LTBs of ICIs achieved durable disease control, with LC-OS approaching 90% at 8 yrs. In these pts, late progression was uncommon, typically involving ≤5 lesions with modest growth kinetics, often treated with local therapy without requiring immediate systemic treatment. The predominance of non-lung cancer mortality suggests that survivorship care addressing second malignancies is increasingly important in this population. Landmark survival analysis from 4 years after ICI initiation (n=235). Timepoint PFS TTNC OS Other Cause OS LC-OS 5-year 90.1% 96.4% 97.2% 97.7% 99.5% 6-year 82.4% 90.3% 91.8% 93.8% 97.8% 7-year 74.6% 81.3% 82.7% 87.3% 94.7% 8-year 69.9% 74.3% 74.5% 84.7% 88.0%