Predictive implications of immune-related adverse events after exposure to VEGF inhibitors on outcomes in patients with advanced NSCLC treated with prior immune check point inhibitor.

8568 Background: Immune-related adverse events (irAEs) have been associated with enhanced antitumor immune activity, potentially correlating with improved clinical outcomes. Implications of delayed irAE after exposure to VEGF inhibitors on clinical outcomes remain poorly defined. We hypothesize that patients who develop irAEs during or following immune checkpoint inhibitors (ICIs) therapy will demonstrate improved overall survival (OS) and progression-free survival (PFS) compared to those who do not develop irAEs. Methods: We conducted a single center retrospective chart review of patients with non-small cell lung cancer (NSCLC) who had received at least one line of immunotherapy and subsequently underwent treatment with ramucirumab upon progression. Patients were categorized based on the presence or absence of irAEs during or after ICIs. 41 patients were identified. Kaplan-Meier estimates and log-rank tests were used for survival analyses, while Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Of 41 identified subjects, median age was 63, 83% had adenocarcinoma, 56% had metastatic disease at presentation and 93% had received previous chemotherapy. Initial immunotherapy received was pembrolizumab 66%, nivolumab 20% and durvalumab 10%. For second line treatment, 85% received ramucirumab with docetaxel. 37% (n=15) of patients experienced irAE after ICIs. From the start of ramucirumab, the median OS was 8.0 months for patients with irAEs versus 6.0 months for those without, and the median PFS was 7.0 months versus 3.0 months, respectively. HRs suggested a trend favoring longer survival for patients with irAEs (HR for PFS = 0.52; 95% CI: 0.25–1.08; p=0.0072 and HR for OS = 0.62; 95% CI: 0.29–1.27; p=0.0192), though not statistically significant. Patients who developed delayed irAEs (after the start of ramucirumab) (n=4, 9.7%) had significantly prolonged OS, 34.5 months (HR 0.22; 95% CI: 0.05–0.94; p=0.0406) and PFS 33.5 month (HR 0.18; 95% CI: 0.043–0.80; p=0.0234) compared to those without. The most common irAEs were colitis (47%), rash (20%), and pneumonitis (13%). Conclusions: Our findings suggest that the occurrence of irAEs during or after immunotherapy may be associated with improved outcomes in patients with advanced NSCLC who receive ramucirumab-based treatment. Although the observed survival benefit for patients with any irAE was not statistically significant, those who developed delayed irAEs after initiating ramucirumab exhibited significant prolongation of OS and PFS. This raises the possibility that delayed irAEs after exposure to VEGF likely suggests a reinvigorated immune response and may serve as a prognostic marker. Further prospective validation in larger patient cohorts is warranted to investigate these findings.