Analysis of patterns of care and benefit of thoracic radiotherapy for patients with stage IV NSCLC in the immunotherapy-era from a national hospital-based registry.

Abstract

9123 Background: Metastatic non-small cell lung cancer (mNSCLC) has classically been treated with platinum-doublet chemotherapy. Recent studies have established immunotherapy as an integral part of therapy for mNSCLC without targetable mutations. There are limited data on the role of consolidative thoracic radiotherapy (TRT) for patients with mNSCLC in the immunotherapy-era. A secondary analysis of KEYNOTE-001 showed significant improvement in overall survival in patients who received radiotherapy with pembrolizumab compared to patients not previously receiving radiotherapy. Methods: We queried the National Cancer Database (NCDB) for patients with metastatic presentation, stage IVA/IVB non-small cell lung cancer between the ages of 18-90 years treated between 2012-2017 with a combination of chemotherapy, immunotherapy, and thoracic radiotherapy. Patients with unknown treatment status, follow up time, or vital status were excluded. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between treatment groups utilizing log-rank testing. A 3:1 nearest-neighbor propensity-score matching was performed utilizing clinical and demographic covariates to reduce the impact of potential confounders of overall survival on the probability of receipt of TRT. Cox proportional hazards regression was used to identify predictors of overall survival. Results: A total of 81,382 patients were identified that met inclusion criteria. The median age was 68 (18-90) years. The majority of patients (n = 51,681, 64%) had chemotherapy, while 7,929 (10%) patients received immunotherapy, and 15,984 (20%) received TRT. The median follow-up was 6.18 (range 0-76.9) months. For the entire cohort of patients receiving immunotherapy, 2 year OS was 29.4% with TRT compared to 32.7% without. Following propensity matching by age, sex, race, and comorbidity score, a total number of 4,264 patients receiving immunotherapy were matched. The 2 year OS was 27.7% in patients receiving TRT and immunotherapy vs. 22.2% in patients with immunotherapy alone (p = 0.004). On multivariable analysis receipt of TRT was a significant predictor of OS after adjustment for age, race, comorbidity score, sex, and median income (p = 0.0003, HR 0.87, 95% CI 0.80 - 0.94). For patients receiving BED10 > 39 Gy (equivalent to 30 Gy in 10 fractions), 2 year OS was significantly improved at 37.0% vs 18.1% (p < 0.0001). Conclusions: In patients with mNSCLC, the addition of TRT to immunotherapy is associated with improved overall survival at 2 years. Receipt of a higher BED10 is associated with further improved survival. Selection of mNSCLC patients receiving immunotherapy for TRT approaching definitive doses warrants further investigation. Data from prospective, randomized trials may better elucidate this benefit and identify a potential mechanism.