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Prophylactic pirfenidone to prevent radiation- induced lung injury in ICI-pretreated lung cancer patients: a phase II study

Year: 2026

Type: article

Abstract: Objective This study aimed to relieve radiation-induced lung injury (RILI) by assessing the use of prophylactic pirfenidone. Subjects were lung cancer patients with prior ICI treatment who received thoracic radiotherapy. Methods Patients with lung cancer were enrolled in this phase II single-arm study. All candidates had a history of prior ICI exposure (≥2 cycles; interval ≤6 months) scheduled for thoracic radiotherapy (≥50 Gy). Patients received oral pirfenidone (1800 mg/day) from one week pre-radiotherapy to four weeks post-completion. The primary endpoint was the 6-month incidence of ≥grade 2 RILI, compared to a 40% historical control (p 0 =0.40; p 1 =0.22; α=0.10; power=80%). Secondary endpoints included pulmonary function (DLCO%, FVC%) and safety. Results A total of 39 patients were enrolled in this trial. At the 6-month follow-up, the incidence of grade 2 or higher RILI was 23.1% (9/39; 95% CI: 11.1%–39.3%). This rate was statistically significantly lower than the 40% incidence from the historical control cohort (p=0.0205). Grade 3 RILI occurred in 7.7% (3/39); no grade 4–5 events occurred. Mean DLCO% declined by 7.6 ± 5.4% at 3 months and 6.5 ± 5.8% at 6 months. The pirfenidone completion rate was 84.6% (median relative dose intensity: 89.3%). Common adverse events were fatigue (43.6%), nausea (41.0%), and appetite loss (33.3%), mostly grade 1–2. Conclusions Preventive use of pirfenidone was associated with a lower observed incidence and severity of RILI than the predefined historical control in ICI-pretreated lung cancer patients receiving thoracic radiotherapy. Additionally, the intervention showed a potential protective trend for pulmonary diffusion function. These findings require further validation in a phase III trial.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1876642