Prophylactic pirfenidone to prevent radiation- induced lung injury in ICI-pretreated lung cancer patients: a phase II study
- 1Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology
- 2Department of Oncology, Jianghan Oilfield General Hospital
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.
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BibTeX
@article{huang2026prophylactic,
title = {{Prophylactic pirfenidone to prevent radiation- induced lung injury in ICI-pretreated lung cancer patients: a phase II study}},
author = {Yujie Huang and Jia Ma and Guang Han and JianPing Bi and Guoliang Pi and Ying Li and Yi Peng and Chuangying Xiao and Xiulin Tuo},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1876642},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1876642/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prophylactic pirfenidone to prevent radiation- induced lung injury in ICI-pretreated lung cancer patients: a phase II study
AU - Yujie Huang
AU - Jia Ma
AU - Guang Han
AU - JianPing Bi
AU - Guoliang Pi
AU - Ying Li
AU - Yi Peng
AU - Chuangying Xiao
AU - Xiulin Tuo
PY - 2026
DA - 2026/10/15
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1876642
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1876642/full
AB - 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.
SN - 2234-943X
ER -