广泛期小细胞肺癌诱导治疗后胸部放疗序贯PD-1/PD-L1抑制剂的安全性研究

Safety of thoracic radiotherapy followed by PD-1/PD-L1 inhibitor after induction therapy for extensive-stage small cell lung cancer

目的评估胸部放疗序贯联合PD-1/PD-L1抑制剂应用于诱导治疗后的广泛期小细胞肺癌(ES-SCLC)的安全性、耐受性。方法前瞻性纳入中国医学科学院肿瘤医院1项Ⅰ期临床试验和1项真实世界研究中的ES-SCLC患者,两项研究均经中国医学科学院肿瘤医院伦理委员会批准,选择其中确诊时为广泛期、经系统治疗(化疗/化疗联合PD-1/PD-L1抑制剂)后、经胸部放疗和序贯PD-1/PD-L1抑制剂的患者入组。结果从2019年1月到2021年3月,共纳入11例ES-SCLC患者,全组年龄52~73岁,中位数62岁。5例患者先接受诱导化疗,6例先接受化疗联合PD-1/PD-L1抑制剂,经评价系统治疗疗效后均接受了胸部调强放疗。2例患者发生了治疗相关3-5级不良反应(1例肺炎和1例放射性食管炎)。常见轻度不良反应主要包括1-2级血液系统不良反应、肺炎和食欲下降,仅1例患者因免疫性肺炎终止免疫治疗。中位随访时间12.5个月(3.5~16.4个月),中位无进展生存和总生存时间分别为7.4个月(95%CI为6.9~8.0个月)和14.6个月(95%CI为9.0~20.2个月)。结论诱导治疗的ES-SCLC患者胸部放疗后序贯PD-1/PD-L1抑制剂治疗安全可行。鉴于胸部放疗和免疫治疗在ES-SCLC治疗中均可带来获益,该综合治疗模式的有效性值得进一步探索。

Objective To evaluate the safety and tolerance of sequential thoracic radiotherapy combined with PD-1/PD-L1 inhibitors in patients with extensive-stage small cell lung cancer(ES-SCLC)after induction systemic therapy.Methods ES-SCLC patients from a phase I trial and a real-world study were enrolled for those who received thoracic radiotherapy after induction systemic treatment(chemotherapy/chemotherapy combined with PD-1/PD-L1 inhibitors)and consolidated with PD-1/PD-L1 inhibitors.These two studies were both approved by the Ethics Committee of Chinese Academy of Medical Sciences Cancer Hospital(Clinical Trials.gov number,NCT03971214,NCT04947774).Results Between January 2019 and March 2021,a total of 11 patients with ES-SCLC were analyzed,aged 52-73 years,with a median age of 62 years.Among them,five patients(45.5%)received induction chemotherapy and six patients(54.5%)received chemotherapy combined with PD-1/PD-L1 inhibitor,and then all received intensity-modulated thoracic radiotherapy after evaluation of systemic treatment efficacy.Two patients developed treatment-related grade G3-5 toxicity(18.2%,1 treatment-related pneumonitis and 1 radiation esophagitis).G1-G2hematologic toxicity,pneumonia,and anorexia were common mild toxicities.Only one patient(9.1%)terminated immunotherapy due to immune-related pneumonitis.During a median follow-up time of 12.5 months(range:3.5-16.4 months),the median disease progression-free survival and overall survival was 7.4 months(95%CI:6.9-8.0 months)and 14.6 months(95%CI:9.0-20.2 months),respectively.Conclusions Sequential thoracic radiotherapy followed by PD-1/PD-L1 inhibitor is safe and feasible in patients with ES-SCLC after induction therapy.Given that both thoracic radiotherapy and immunotherapy benefits the ES-SCLC in survival,this comprehensive treatment modality warrants further investigation.