276 - Pirfenidone for Reducing Radiation-Induced Lung Injury in Lung Cancer Patients with Prior Receipt of Immune Checkpoint Inhibitors: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial
Presenter(s)
G. Han1, G. Pi1, Y. Li1, M. Zhai1, X. Tuo2, Y. Li1, H. He1, H. Shi1, V. Verma3, J. Qian4, J. Bi1, and C. Lin5; 1Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Wuhan, China, 2Department of Oncology, Jianghan Oilfield General Hospital, Qianjiang, China, Qianjiang, China, 3Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst, MA, USA, Amherst, MA, 5Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE
Purpose/Objective(s): Multiple studies indicate that thoracic radiotherapy (TR) administered following immune checkpoint inhibitors (ICIs) elevates the risk of radiation-induced lung injury (RILI) (grade =2 incidence approximately 40%). Pirfenidone is an orally active, broad-spectrum antifibrotic inhibitor of the cytokine TGF-ß that inhibits the biological activity of fibroblasts and reduces matrix collagen synthesis, which effectively slows disease progression in patients with idiopathic pulmonary fibrosis. We conducted a phase II trial evaluating the efficacy and safety of pirfenidone for reducing RILI in lung cancer patients with prior receipt of ICIs.
Materials/Methods: This single-arm, multicenter, open-label, phase II trial enrolled patients who received pirfenidone during TR by using Simon’s two-stage design implemented via the R package gen2stage, planning a total sample size of 41 patients and defining trial success as fewer than 13 cases of grade =2 RILI among the 41 patients. Eligible lung cancer patients were 18 or older, had a Zubrod performance status of 0–1, had received at least 2 cycles of ICIs along with TR (=50Gy biologically effective dose assuming a/ß 10). Pirfenidone was given on the first day of TR orally three times daily at doses of 200 mg in week 1, 300 mg in week 2, and 400 mg in weeks 3-12. The primary endpoint was the incidence of grade =2 RILI. Safety was assessed in all participants who received at least one dose of pirfenidone.
Results: Between March 20, 2023, and July 3, 2025, a total of 41 patients were enrolled from two institutions, all of whom completed TR. ICIs (median 5 cycles, IQR: 3-6) were PD-1 (82.9%) or PD-L1 (16.1%) inhibitors; TR commenced at a median of 27 days (IQR, 24-36) thereafter. 36.6% of patients received concurrent chemoradiotherapy, and the median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR, 60-60.8 Gy). The median GTV volume, V30, V20, V5, and Dmean (lungs) were 193.9cm3, 13.9%, 20.1%, 39.2% and 11.3Gy, respectively. The median follow-up was 16.7 months (IQR: 9.7-21). The incidence rate of grade =2 RILI was 26.8% (Grade 2, 3, 4, 5 were 14.6%, 9.8%, 0%, and 2.4%, respectively). A one-sided binomial test (H0: p=0.4) yielded P=0.053 (<0.1 (preset a)). The most common drug adverse reactions related (TRAE) to pirfenidone were nausea (19.5%) and skin itching (9.8%). There were no drug treatment related deaths.
Conclusion: Pirfenidone during TR exhibits good tolerability and encouragingly low rates of grade =2 RILI in patients with prior exposure to immunotherapy. Additional prospective studies are needed to validate these findings. (NCT05801133)