Outcomes in Patients With Metastatic Lung Cancer Receiving PD-1/PD-L1 Inhibitors With Thoracic Radiotherapy


Key Points

  • Thoracic radiotherapy was not associated with a higher risk of pneumonitis or other symptomatic immune-related adverse events in patients with metastatic lung cancer treated with PD-1 or PD-L1 inhibitors.
  • Thoracic radiotherapy was associated with a nonsignificant reduction in the risk of all-cause mortality. 

In a research letter to JAMA Oncology, Hwang et al detailed the outcomes of patients with metastatic lung cancer receiving an inhibitor of programmed cell death protein 1 (PD-1) or its ligand (PD-L1) with or without thoracic radiotherapy at Massachusetts General Hospital.

Study Details

The analysis included 164 patients treated between 2013 and 2016; 158 had non–small cell lung cancer and 6 (5%) had small cell lung cancer. Of them, 73 received thoracic radiotherapy and 91 did not; the 2 groups had similar baseline characteristics except for a lower proportion of patients in the radiotherapy cohort having adenocarcinoma (49% vs 75%) and targetable mutations (EGFR/ALK/ROS1; 4% vs 16%). Outcomes of interest were immune-related adverse events and survival.

Immune-Related Adverse Events

There were no significant differences between the radiotherapy group and the no-radiotherapy group with regard to the rates of grade ≥ 2 immune-related adverse events (13.7% vs 15.4%, P = .83), any-grade pneumonitis (8.2% vs 5.5%, P = .54), or grade ≥ 2 pneumonitis (4.1% vs 3.3%, P > .99). In the radiotherapy group, the median radiotherapy dose was similar in those patients who did vs did not develop pneumonitis (52.8 vs 50.4 Gy, P = .76). Of the 73 patients, 57 were treated with radiotherapy before checkpoint inhibitor initiation; pneumonitis did not occur in any of the 16 patients receiving radiotherapy between checkpoint inhibitor cycles or after treatment or receiving more than 1 course of radiotherapy.

Survival Findings

In the entire group, median overall survival was 12.1 months. On a multivariate analysis, all-cause mortality was lower in patients with grade ≥ 2 immune-related adverse events (hazard ratio [HR] = 0.45, P = .03) and in those receiving fewer chemotherapy lines (HR as continuous variable = 1.21, P = .01). Receipt of thoracic radiotherapy was associated with a nonsignificant reduction in all-cause mortality (HR = 0.66, P = .06).

The investigators concluded: “[P]ending prospective validation, our results suggest that [thoracic radiotherapy] does not significantly increase the risk of symptomatic [immune-related adverse events], including pneumonitis, compared with [checkpoint inhibitors] alone.”

Florence K. Keane, MD, of the Department of Radiation Oncology, Massachusetts General Hospital, is the corresponding author of the JAMA Oncology article.

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