Abstract
BackgroundPreclinical studies suggest enhanced anti-tumor activity with combined radioimmunotherapy. We hypothesized that radiation (RT) + immunotherapy would associate with improved overall survival (OS) compared to immunotherapy or chemotherapy alone for patients with newly diagnosed metastatic non-small-cell lung cancer (NSCLC).MethodsThe National Cancer Database was queried for patients with stage IV NSCLC receiving chemotherapy or immunotherapy from 2013 to 2014. RT modality was classified as stereotactic radiotherapy (SRT) to intra- and/or extracranial sites or non-SRT external beam RT (EBRT). OS was analyzed using the Kaplan-Meier method and Cox proportional hazards models.ResultsIn total, 44,498 patients were included (13% immunotherapy, 46.8% EBRT, and 4.7% SRT). On multivariate analysis, immunotherapy (hazard ratio [HR]:0.81, 95% confidence interval [CI]:0.78–0.83) and SRT (HR:0.78, 95%CI:0.70–0.78) independently associated with improved OS; however, the interaction term for SRT + immunotherapy was insignificant (p = 0.89). For immunotherapy patients, the median OS for no RT, EBRT, and SRT was 14.5, 10.9, and 18.2 months, respectively (p < 0.0001), and EBRT (HR:1.37, 95%CI:1.29–1.46) and SRT (HR:0.78, 95%CI:0.66–0.93) associated with OS on multivariate analysis. In the SRT subset, median OS for immunotherapy and chemotherapy was 18.2 and 14.3 months, respectively (p = 0.004), with immunotherapy (HR:0.82, 95%CI:0.69–0.98) associating with OS on multivariate analysis. Furthermore, for patients receiving SRT, biologically effective dose (BED) > 60 Gy was independently associated with improved OS (HR:0.79, 95%CI:0.70–0.90, p < 0.0001) on multivariate analysis with a significant interaction between BED and systemic treatment (p = 0.008).ConclusionsTreatment with SRT associated with improved OS for patients with metastatic NSCLC irrespective of systemic treatment. The high survival for patients receiving SRT + immunotherapy strongly argues for evaluation in randomized trials.
Highlights
Preclinical studies suggest enhanced anti-tumor activity with combined radioimmunotherapy
Compared to the chemotherapy group, the immunotherapy group contained a larger proportion of female patients, younger patients, and patients with adenocarcinoma histology
The median dose for patients receiving external beam RT (EBRT) was 30 Gy in a median of 10 fractions while the median dose for patients receiving stereotactic radiotherapy (SRT) was 22 Gy in a median of a single fraction (IQR: 1–4)
Summary
Preclinical studies suggest enhanced anti-tumor activity with combined radioimmunotherapy. We hypothesized that radiation (RT) + immunotherapy would associate with improved overall survival (OS) compared to immunotherapy or chemotherapy alone for patients with newly diagnosed metastatic non-small-cell lung cancer (NSCLC). Patients with any history of predominantly intracranial (61%) RT receiving pembrolizumab for advanced NSCLC had improved OS in a secondary analysis of the phase I KEYNOTE-001 trial [10]. These data combined with promising preclinical observations [11, 12] and the theoretical advantages of combined radioimmunotherapy [13] have promoted enthusiasm for concurrent or sequential RT plus immunotherapy in advanced NSCLC. We hypothesized that RT plus immunotherapy would associate with improved OS for patients with stage IV NSCLC in the National Cancer Database (NCDB) and further examined the influence of RT technique and dose on OS
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