High radiation dose in chemoradiotherapy followed by immunotherapy with durvalumab in patients with stage III non-small cell lung cancer does not increase risk for pneumonitis

PURPOSE: Consolidation immunotherapy with immune checkpoint Inhibitor (ICI) Durvalumab is an effective treatment for inoperable stage III non-small cell lung cancer (NSCLC) patients with a PD-L1 expression ≥ 1% after definitive curative concurrent chemoradiotherapy (CCRT). While this approach is widely used as standard therapy, it carries an increased risk of immune-related and radiation-induced pneumonitis. Currently, there is no data on pneumonitis in patients receiving CCRT with an overall dose of 70 Gy (Gy) compared with the standard protocol of 60 Gy ± 10% in this setting.

METHODS: This study analyzed retrospective data from 39 patients with unresectable NSCLC treated with CCRT. Patients received either 70 Gy (n = 29) or lower than 70 Gy total dose (n = 10) in 2 Gy fractions. Cases of pneumonitis were further classified as RI‑P (Radio-induced Pneumonitis) and ICI‑P (ICI Pneumonitis) based on clinical and radiological findings.

RESULTS: Of the 39 patients, 15 (38.5%) developed pneumonitis, with 10 out of 29 (34.5%) in the 70 Gy group and five out 10 (50%) in the < 70 Gy group. There was no significant difference in pneumonitis and in occurrence of ICI‑P vs. RI‑P (26.7% vs. 73.3%) within both groups. The 70 Gy group showed a significant benefit in mortality (p = < 0.001). Overall survival (OS) differed significantly between groups (p =0.028).

CONCLUSIONS: 70 Gy radiation dose for CCRT followed by durvalumab is a safe regimen and may provide clinical benefits in NSCLC patients compared to lower doses. Pneumonitis incidence aligns with previous literature. The higher dose is associated with improved overall survival, and reduced disease progression, potentially due to a longer consolidation time.