Immune checkpoint blockade in the treatment of advanced non-small cell lung cancer – predictors of response and impact of previous radiotherapy

Abstract

Background The implementation of immune checkpoint inhibitors (ICI) into the standard care of advanced non-small cell lung cancer (NSCLC) has improved prognosis for this group of patients. However, long-term survival is rare. The aim of the study was to identify predictors of response and, especially, to investigate the impact radiotherapy might have on duration of response. Material and methods The association between pretreatment patient/tumor characteristics and progression-free survival (PFS), overall survival (OS), and lung cancer-specific survival was investigated in 78 patients receiving an ICI as ≥2nd line treatment for advanced NSCLC, using Cox regression analysis. Due to competing risk, cause-specific deaths were also examined with cumulative incidence plots. Results Median OS was 12.6 months (95% CI 7.8–18.2) and median PFS 4.1 months (95% CI 3.0–6.2), after median follow-up time of 49.7 months (range 20.9–51.5). Increasing CRP and neutrophil/lymphocyte ratio (NLR), were associated with poor PFS (CRP: HR 1.49, 95% CI 1.12–1.98; NLR: HR 1.59, 95% CI 1.22–1.85) and OS (CRP: HR 1.94, 95% CI 1.47–2.56; NLR: HR 1.54, 95% CI 1.27–1.87). Radiotherapy prior to immunotherapy was not significantly associated with patient outcome. However, when the dataset was split at 6 months of follow-up, to be able to identify early and late predictors of prognosis, we found that patients receiving radiotherapy <6 months prior to immunotherapy had better PFS (HR: 0.27, 95% CI 0.09–0.84) and lung cancer-specific survival (HR: 0.41, 95% CI 0.18–0.95) after the first 6 months of follow-up, while increasing CRP (PFS: HR1.61, 95% CI 1.21–2.14; OS: HR2.04, 95% CI 1.51–2.74) and NLR (PFS: HR 1.57, 95% CI 1.29–1.91; OS: HR 1.63, 95% CI 1.35–1.97) were predictors of poor short-term prognosis. Conclusions Radiotherapy may be of importance to achieve a long-lasting response to immunotherapy, while indicators of systemic inflammation can help in identifying patients with poor short-term prognosis.