Addition of Pirfenidone to Glucocorticoids in Grade 2 or 3 Radiation-Induced Lung Injury

In a Chinese phase II trial reported in The Lancet Oncology, Hou et al found that the addition of the antifibrotic pirfenidone to glucocorticoid treatment significantly improved the carbon dioxide diffusing capacity (DLCO%) in patients with grade 2 or 3 radiation-induced lung injury.

Study Details

In the multicenter open-label trial, 134 patients were randomly assigned between November 2021 and December 2023 to receive pirfenidone plus glucocorticoids (n = 67) or glucocorticoids alone (n = 67). Pirfenidone treatment consisted of three times daily dosing of 200 mg in week 1, 300 mg in week 2, and 400 mg in weeks 3 to 24. Glucocorticoid treatment consisted of the prednisone equivalent of 40 mg per day in two doses for 2 weeks, followed by tapering to 10 mg every 2 weeks over 6 to 8 weeks. The primary endpoint of the study was the change in DLCO% at week 24.

Key Findings

Median follow-up was 9.2 months. At week 24, changes in DLCO% were an improvement of 8.0% in the pirfenidone group vs a reduction of 2.4% in the control group (least-squares mean difference = 10.4%, 95% confidence interval [CI] = 4.3%–16.5%, P = .0010). Numeric improvement in DLCO% at week 24 was observed in 78% vs 54% of patients.

The most common adverse event of any grade among all patients was pneumonia (9% in the pirfenidone group vs 25% in the control group). The most common grade 3 or worse adverse events included pneumonia (6% vs 12%) and rash (3% vs 0%). Serious adverse events occurred in 18% vs 16% of patients. No treatment-related deaths were reported.

The investigators concluded: “Pirfenidone in combination with glucocorticoids provides a potential therapeutic strategy for grade 2 or grade 3 radiation-induced lung injury, addressing the unmet clinical need for effective antifibrotic therapy in patients receiving thoracic radiotherapy. Further investigation is needed to validate these findings in patients with worse radiation-induced lung injury than was studied here.”

Ming Chen, MD, of State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the Noncommunicable Chronic Diseases–National Science and Technology Major Project, National Key R&D Program of China, and others. For full disclosures of all study authors, visit thelancet.com.