Background: In the landmark PACIFIC trial, 6.3% of patients with unresectable stage III NSCLC receiving durva after chemoradiation developed mCNS. Data on incidence of mCNS in non-clinical trial patient populations are needed to evaluate CNS surveillance strategies. Methods: We conducted a retrospective study of patients with unresectable stage III NSCLC treated with durva following chemoradiation from 2018 to 2021 with baseline CNS imaging showing no mCNS. Patient characteristics and outcomes were assessed, including age, tumor histology, stage, mCNS incidence, and survival. OS was calculated from date of initiation of durva to death or censored at last follow-up. Results: Out of 86 patients included in our study, a total of 17 (19.8%) developed mCNS after starting durva. Development of mCNS was not associated with age, sex, histology, T or N staging or PD-L1 expression (Table 1). Three patients (3.5%) had CNS-only metastases whereas 14 (16.3%) had progression outside the CNS. The median time from baseline CNS imaging to first durva was 3.8 months (IQR 3.0 – 4.9) in the cohort. The median time from first durva to development of mCNS was 4.7 months (IQR 2.3 – 8.7). Median OS in patients with mCNS was 15.2 months (95% CI 8.6 – 25.9) compared to 36.9 months (95% CI 27.2 – NR) in patients without mCNS (p = 0.010). Conclusions: Incidence of mCNS among a cohort of patients with stage III NSCLC managed with durva after chemoradiation was 19.8% which is higher than that observed in landmark clinical trials. The OS for patients with mCNS was shorter than those without mCNS. Most mCNS occurred within 6 months of starting durva and were often accompanied by systemic progression. Further research is needed to understand optimal surveillance strategies for mCNS in this patient population.

CNS = Central nervous system, IQR = interquartile range, PDL1 = programmed cell death ligand-1. *T stage data was missing for 6 patients that did not develop mCNS. **PDL1 expression data was missing for 12 patients who did not develop mCNS.