Impact of Radiotherapy on the Efficacy and Toxicity of anti-PD-1 Inhibitors in Metastatic NSCLC

Clin Lung Cancer. 2021 May;22(3):e425-e430. doi: 10.1016/j.cllc.2020.06.001. Epub 2020 Jun 10.

Abstract

Background: The impact of radiotherapy (RT) on the efficacy and toxicity of immune checkpoint inhibitors (ICIs) in patients with metastatic non-small-cell lung cancer (NSCLC) is unclear.

Materials and methods: We identified patients with metastatic NSCLC treated with the anti-programmed death 1 antibodies nivolumab or pembrolizumab between January 2016 and May 2019 at 3 tertiary centers, who were also treated with palliative RT either during or within 3 months of starting anti-programmed death 1 treatment. Patient demographics, tumor characteristics, and treatment history were collected. Response rates, progression-free survival (PFS), and overall survival (OS) were analyzed and correlated with RT use.

Results: A total of 269 patients were identified, with a median follow-up of 19.4 months. The median age was 70 years (range, 35-90 years), and they were 63% male, 60% smokers, and 65% had adenocarcinoma histology. At the commencement of ICI treatment, the majority (86%) had ≥ 1 line of prior therapy and 34% had brain metastases. A total of 102 (38%) patients 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% confidence interval, 1.3-2.6 months) and the median OS was 9.0 months (95% confidence interval, 6.4-9.5 months). There were no significant differences in median PFS (3.0 vs. 2.0 months; P = .515) and median OS (9.0 vs. 9.0 months; P = .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.

Keywords: Abscopal effect; Immune related adverse events; Immunotherapy; Metastatic NSCLC; anti- PD-1 inhibitors.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Immune Checkpoint Inhibitors / adverse effects
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Nivolumab / administration & dosage
  • Nivolumab / adverse effects
  • Palliative Care / methods*
  • Progression-Free Survival
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Immune Checkpoint Inhibitors
  • Nivolumab
  • pembrolizumab