Risk factors and incidence of pneumonitis in NSCLC patient treated with chemoradiotherapy and Durvalumab: A comparative analysis with a non-Durvalumab cohort (PraDa).

BACKGROUND

Concurrent chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small cell lung cancer (NSCLC). In patients without progression, adjuvant Durvalumab, an anti-PD-L1 antibody, improves survival but raises concerns about iatrogenic pneumonitis (radiation-induced or immune-mediated). This study aimed to assess the incidence and identify predictive factors of grade ≥2 (G2+) iatrogenic pneumonitis in patients treated with or without Durvalumab.

MATERIALS AND

METHODS

We conducted an ambispective cohort study across five hospitals between January 2019 and December 2020. Patients with unresectable, locally advanced NSCLC treated with concurrent chemoradiotherapy with or without Durvalumab were included. Iatrogenic pneumonitis was diagnosed based on clinical and radiological criteria, excluding alternative causes. The primary endpoint was the 2-year cumulative incidence of G2+ iatrogenic pneumonitis after radiotherapy.

RESULTS

Ninety-one patients were included: 57 in the Durvalumab group and 34 in the control group. Grade ≥ 2 iatrogenic pneumonitis occurred in 30% of patients receiving Durvalumab and 24% of those without (p = 0.5). In the complete cohort, significant interactions between durvalumab treatment and female sex (p = 0.05), total radiotherapy dose (p = 0.03), and mean heart dose (p = 0.04) were observed for the risk of pneumonitis.

CONCLUSION

The addition of Durvalumab to chemoradiotherapy did not significantly increase the incidence of G2+ iatrogenic pneumonitis. However, the identification of female sex, total radiation dose, and mean heart dose as potential risk factors highlights the need for personalized monitoring. Prospective validation is warranted.