Impact of radiotherapy on the efficacy and toxicity of anti-PD-1 inhibitors in metastatic NSCLC

Abstract Background The impact of radiotherapy (RT) on the efficacy and toxicity of immune checkpoint inhibitors (ICI) in patients (pts) with metastatic non-small cell lung cancer (NSCLC) is unclear. Materials & Methods We identified patients with metastatic NSCLC treated with the anti-programmed death 1 (PD-1) antibodies nivolumab or pembrolizumab between January 2016 and May 2019 at three tertiary centers who were also treated with palliative RT either during or within 3 months of starting anti-PD1 treatment. Patient demographics, tumour characteristics, and treatment history were collected. Response rates, progression-free survival (PFS) and overall survival (OS) were analysed and correlated with RT use. Results A total of 269 patients were identified, with median follow up of 19.4 months. The median age was 70 years (range 35-90), 63% male, 60% smokers and 65% had adenocarcinoma histology. At the commencement of ICI treatment, majority (86%) had ≥1 line of prior therapy and 34% had brain metastases. 102 patients (38%) received RT within 3 months of starting ICI or subsequently during ICI treatment. Of patients that received RT, 86 (84%) received conventional hypofractionated RT, and in the majority 81 (79%) the intent of RT was symptom control. The use of RT did not increase grade 3/4 immune-related adverse events. The overall median PFS was 2.0 months (95% CI 1.3 – 2.6 months) and median OS was 9.0 months (95% CI 6.4 – 9.5 months). There were no significant differences in median PFS (3.0 vs 2.0 months, p=0.515) and median OS (9.0 vs 9.0 months, p=0.917) in the patients who received RT versus those that did not. Conclusions In patients with metastatic NSCLC, the addition of RT to ICI was not associated with increased toxicity or improved survival.