Pirfenidone for grade 2 and grade 3 radiation-induced lung injury: a multicentre, open-label, randomised, phase 2 trial.

Pirfenidone, an oral antifibrotic drug that is often used to treat idiopathic pulmonary fibrosis, could offer therapeutic benefits for patients with radiation-induced lung injury.

吡非尼酮是一种常用于治疗特发性肺纤维化的口服抗纤维化药物，可能为放射性肺损伤患者提供治疗益处。

We evaluated the efficacy and safety of pirfenidone in patients with grade 2 or grade 3 radiation-induced lung injury.

我们评估了吡非尼酮在2级或3级放射性肺损伤患者中的疗效和安全性。

Methods

This multicentre, open-label, randomised, phase 2 clinical trial enrolled patients with grade 2 or grade 3 radiation-induced lung injury diagnosed according to Common Terminology Criteria for Adverse Events version 5.0 from ten medical centres across China.

这项多中心、开放标签、随机的2期临床试验，根据不良事件通用术语标准第5.0版，从中国十家医疗机构招募了2级或3级放射性肺损伤患者。

Eligible patients were aged 18-75 years with an Eastern Cooperative Oncology Group performance status of 0-2 and had grade 2 or grade 3 radiation-induced lung injury.

符合入选标准的患者年龄在18至75岁之间，东部肿瘤协作组表现状态评分为0-2，并且有2级或3级放射性肺损伤。

Patients were randomly assigned (1:1) using a computer-generated random number table to receive either pirfenidone plus glucocorticoids or glucocorticoids alone.

患者使用计算机生成的随机数字表以1:1的比例随机分配，接受吡非尼酮加糖皮质激素或仅糖皮质激素治疗。

Pirfenidone was given orally three times daily at doses of 200 mg in week 1, 300 mg in week 2, and 400 mg in weeks 3-24.

吡非尼酮口服给药，每日三次，第1周剂量为200 mg，第2周为300 mg，第3-24周为400 mg。

Glucocorticoids were administered concurrently at the equivalent dose of prednisone 40 mg/day, divided into two oral doses, and maintained for 2 weeks, followed by a tapering schedule of 10 mg every 2 weeks over a period of 6 to 8 weeks.

同时给予相当于泼尼松40 mg/天的糖皮质激素，分为两次口服剂量，并维持2周，随后按照每2周减少10 mg的递减方案，在6到8周内逐渐减量。

The control group received glucocorticoids only.

对照组仅接受糖皮质激素治疗。

The primary endpoint, evaluated in the modified intention-to-treatpopulation, was the change in the percentage of carbon monoxide diffusing capacity (DLCO%) from baseline to week 24.

主要终点是在修改后的意向治疗人群中评估的，即从基线到第24周一氧化碳扩散能力（DLCO%）的百分比变化。

Safety was assessed in all participants who received at least one dose of treatment.

所有至少接受一次治疗剂量的参与者均进行了安全性评估。

The trial is registered with ClinicalTrials.gov, NCT03902509, and has completed enrolment.

该试验已在ClinicalTrials.gov注册，注册号为NCT03902509，并已完成招募。

Results

Between Nov 29, 2021, and Dec 4, 2023, 134 patients were enrolled and randomly assigned, with 67 patients in each group study group. 105 (78%) of 134 patients were male and 29 (22%) were female.

在2021年11月29日至2023年12月4日期间，共有134名患者被纳入并随机分配，每组研究组各有67名患者。134名患者中，105名（78%）为男性，29名（22%）为女性。

The median follow-up was 9·2 months (IQR 6·3-16·0).

中位随访时间为9.2个月（四分位数间距6.3-16.0）。

At week 24, the pirfenidone group showed an 8·0% improvement from baseline in DLCO%, whereas the control group showed a 2·4% reduction (least squares mean difference 10·4%, 95% CI 4·3-16·5; p=0·0010).

在第24周时，吡非尼酮组的DLCO%从基线改善了8·0%，而对照组则下降了2·4%（最小二乘均值差异为10·4%，95%置信区间为4·3-16·5；p=0·0010）。

The most common grade 3 or worse adverse events included pneumonia (four [6%] of 67 patients in the pirfenidone group vs eight [12%] of 67 patients in the control group), and rash (two [3%] of 67 patients in the pirfenidone group vs none in the control group).

最常见的3级或更严重的不良事件包括肺炎（吡非尼酮组67名患者中有4名[6%]，对照组67名患者中有8名[12%]）和皮疹（吡非尼酮组67名患者中有2名[3%]，对照组无）。

Serious adverse events occurred in 12 (18%) of 67 patients in the pirfenidone group and 11 (16%) of 67 patients in the control group.

在67名接受吡非尼酮治疗的患者中，有12名（18%）发生了严重不良事件；而在对照组的67名患者中，有11名（16%）发生了严重不良事件。

There were no treatment related deaths.

没有治疗相关的死亡病例。

interpretation

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.

吡非尼酮联合糖皮质激素为2级或3级放射性肺损伤提供了一种潜在的治疗策略，解决了接受胸部放疗患者有效抗纤维化治疗的未满足临床需求。

Further investigation is needed to validate these findings in patients with worse radiation-induced lung injury than was studied here.

需要进一步研究以验证在本研究中所研究的放射性肺损伤更严重的患者中这些发现的有效性。

funding

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.

非传染性慢性疾病-国家科技重大专项、国家重点研发计划、国家自然科学基金以及中山大学肿瘤防治中心癌症创新研究计划。