TOPLINE:

In a phase 2 trial, the addition of pirfenidone to standard glucocorticoids improved pulmonary function, fibrosis, and cough symptoms in patients with grades 2-3 radiation-induced lung injury.

METHODOLOGY:

• Radiation‑induced lung injury is a major dose-limiting toxicity in thoracic radiotherapy. Standard glucocorticoids can treat early-stage inflammation but not later-stage fibrosis. The oral antifibrotic pirfenidone, which is used for idiopathic pulmonary fibrosis, could offer an additional option for treating radiation‑induced lung injury.
• Researchers conducted a multicenter, open-label phase 2 randomized controlled trial to assess the efficacy and safety of pirfenidone in 134 patients with grades 2-3 radiation-induced lung injury.
• Patients were randomly assigned to receive either pirfenidone plus glucocorticoids (n = 67) or glucocorticoids alone (n = 67). Pirfenidone was administered orally three times daily at 200 mg during week 1, 300 mg during week 2, and 400 mg during weeks 3-24. Glucocorticoids were given at a prednisone-equivalent dose of 40 mg per day for 2 weeks and then tapered by 10 mg every 2 weeks over 6-8 weeks.
• The primary endpoint was the change in the percent-predicted diffusing capacity of the lung for carbon monoxide from baseline to week 24. Secondary endpoints were changes in the percent-predicted forced vital capacity (FVC%), percent predicted forced expiratory volume in 1 second (FEV₁%), symptom scores, and radiation-induced lung injury scores. Endpoints were evaluated in a modified intention-to-treat population (60 patients receiving pirfenidone and 63 control individuals), with a median follow-up of 9.2 months.

TAKEAWAY:

• The diffusing capacity of the lung for carbon monoxide improved significantly. At week 24, the least-squares mean change increased by 8% in the pirfenidone group, whereas it decreased by 2.4% in the control group (least-squares mean difference, 10.4%; P = .0010). Overall, diffusing capacity improved in 78% of patients in the pirfenidone group compared with 54% in the control group.
• Both FVC% and FEV1% significantly increased in the pirfenidone group vs the control group (FVC%: 6.1% vs -2.8%; absolute difference, 8.9%; P = .0030; and FEV₁%: 2.4% vs -4.3%; absolute difference, 6.7%; P = .034). By week 24, FVC% improved in 74% of pirfenidone patients compared with 56% of those in the control group; FEV₁% improved in 61% of patients receiving pirfenidone compared with 48% of those in the control group.
• Cough, as well as radiation-induced pulmonary fibrosis, were alleviated more often with pirfenidone. The rate of 24-week acute pulmonary exacerbation-free survival was significantly higher in the pirfenidone vs control group (81.7% vs 61.9%; absolute difference, 19.8%; P = .0017).
• Serious adverse events occurred in 18% of patients on pirfenidone and 16% of control patients, with no treatment‑related deaths. Pneumonia of grade 3 or higher occurred in 6% of patients in the pirfenidone group compared with 12% in the control group. Other serious adverse events in the pirfenidone group were one case each of weight loss, COVID, cerebral edema, coronary artery disease, pulmonary embolism, and intestinal obstruction; only the case of weight loss was considered to be related to the drug.

IN PRACTICE:

This study “provides preliminary evidence that pirfenidone could improve pulmonary function and reduce acute exacerbations in patients with grade 2-3 radiation-induced lung injury, with an acceptable safety profile,” the authors wrote. They added, however, that the findings require validation in larger trials, particularly for patients with grade 3 or worse radiation-induced lung injury.

SOURCE:

The study, led by Zan Hou, Sun Yat-sen University Cancer Center, Guangzhou, China, was published online in The Lancet Oncology.

LIMITATIONS:

The dropout rate exceeded expectations, with tumor progression and death considered dropout events rather than endpoint events. The study did not determine the optimal duration and dosage of pirfenidone for treating radiation-induced lung injury. Additionally, since most patients had grade 2 radiation-induced lung injury, the efficacy of pirfenidone in grade 3 or more severe cases remains unclear.

DISCLOSURES:

Beijing Continent Pharmaceuticals supplied pirfenidone free of charge. The study received support from the Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, National Natural Science Foundation of China, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.