A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non-Small Cell Lung Cancer

Clin Lung Cancer. 2021 Jul;22(4):268-273. doi: 10.1016/j.cllc.2021.01.012. Epub 2021 Jan 25.


Introduction/background: This study assessed the safety and systemic (abscopal) response from the addition of local stereotactic body radiation therapy (SBRT) to checkpoint inhibitor (CPI) immunotherapy in patients with metastatic non-small cell lung cancer.

Patients/methods: Thirty-five patients with at least 2 sites of measurable disease on PET/CT received standard-of-care CPI immunotherapy alone (n = 19), or in combination with 4 cycles doublet carboplatin/pemetrexed chemotherapy (n = 16), and 3 to 5 fractions SBRT to a single extracranial target lesion between cycles 1 to 2 of the systemic therapy. Adverse events were assessed using CTCAE version 5.0. Best systemic objective response rate (ORR) was assessed using iRECIST criteria, excluding any irradiated lesion(s). Additional SBRT to a different target lesion was offered to patients who continued on immunotherapy with unconfirmed progressive disease or mixed response.

Results: Fifteen patients (44%) experienced 22 grade 1 to 2 toxicities potentially attributable to radiation, most commonly pneumonitis (n = 9) and fatigue (n = 6), and no grade 3 to 5 radiation-induced toxicities. Patients undergoing combined CPI-chemotherapy received a lower median biologically effective dose of SBRT than those undergoing CPI monotherapy (43.2 vs. 60Gy), but had a higher rate of radiation-induced toxicity (56% vs. 32%, P < .01). The best systemic ORR was 53%, with 20.5% stable disease and 26.5% progressive disease. Fifteen patients underwent a subsequent course of SBRT based on their response, among which 3 (20%) had progression-free intervals of 12, 16, and 10 months thereafter.

Conclusions: Addition of SBRT to CPI immunotherapy (with/without chemotherapy) is safe. The favorable systemic response observed warrants further assessment with a randomized trial.

Trial registration: ClinicalTrials.gov NCT03137771 NCT03721341.

Keywords: Immune Checkpoint Blockers; Immune Checkpoint Inhibitor; Immunotherapy; Metastatic; Non–small cell lung cancer; PD-L1 inhibitor; Programmed Death-Ligand 1 Inhibitors; Radiation therapy; Radiobiology.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Combined Modality Therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Positron Emission Tomography Computed Tomography
  • Progression-Free Survival
  • Prospective Studies
  • Radiosurgery / adverse effects
  • Radiosurgery / methods
  • Treatment Outcome


  • Immune Checkpoint Inhibitors

Associated data

  • ClinicalTrials.gov/NCT03137771
  • ClinicalTrials.gov/NCT03721341