Purpose: Evaluation of predictors and outcomes in NSCLC patients treated with an immune checkpoint inhibitor (ICI) following a severe immune-related adverse event (irAE). Methods: We included all NSCLC patients receiving ≥1 ICI cycle and corticosteroids for CTCAE Grade ≥3 irAEs between 2017 and 2023 from three UK NHS teaching hospitals. Progression-free survival (PFS) and overall survival (OS) after the 1st irAE, best overall response (BOR) to ICI, and predictors of clinical benefit were evaluated. Kaplan–Meier, Cox and logistic regression models, and Wilcoxon tests were used. Results: We screened 1658 NSCLC patients and identified 80 eligible subjects. The majority of patients had metastatic (n = 50, 63%) vs. localized (n = 30, 37%) NSCLC. Most patients developed a single ≥Grade 3 irAE on 1st line ICI (n = 71, 89%). Overall, 14 (18%) patients developed 2nd irAEs, 7 after rechallenge with ICIs. In the complete cohort, median OS after 1st irAE was 15.84 months (95% CI, 12.45–26.91). Lower neutrophil-to-lymphocyte ratio (NLR), patients receiving >4 cycles of ICI or median duration of ICI of >2.76 months before 1st irAE were associated with improved OS (p < 0.05), the latter two with PFS (p < 0.05). Age, gender, stage, KRAS mutation, PD-L1 and ICI type were not associated with PFS or OS. Pneumonitis as 1st irAE had the worst PFS and OS (p < 0.05). Median starting corticosteroid dose of ≤60 mg for 1st irAE had an improved OS (p = 0.04). Post 1st irAE response associated with better PFS and OS (p < 0.05). Number and duration of irAEs and additional immunosuppressive agents (14% of patients) were not associated with PFS or OS. Conclusions: In ≥Grade 3 irAEs patients managed with corticosteroids, lower baseline NLR, longer ICI use, response to ICI after 1st irAE, and a ≤60 mg corticosteroid dose had promising outcomes.

Background: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy’s Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. Methods: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. Results: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). Conclusions: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients.