帕博利珠单抗辅助治疗完全切除的具有微乳头或实体组织学亚型的Ⅰ期肺腺癌：一项单中心、单臂、2期试验。
Adjuvant pembrolizumab therapy for completely resected stage I lung adenocarcinoma with micropapillary or solid histological subtypes: a single-center, single-arm, phase 2 trial.
作者信息
Kim Jhingook, Bang Yeong Hak, Park Sehhoon, Jung Hyun-Ae, Sun Jong-Mu, Ahn Jin Seok, Ahn Myung-Ju, Jeon Yeong Jeong, Lee Junghee, Cho Jong Ho, Kim Hong Kwan, Choi Yong Soo, Zo Jae Ill, Shim Young Mog, Kang Jung Hee, Lee Jinseon, Choi Yoon-La, Han Joungho, Hwang Soohyun, Lee Ho Yun, Lee Se-Hoon
机构信息
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
出版信息
EClinicalMedicine. 2025 Jun 4;84:103282. doi: 10.1016/j.eclinm.2025.103282. eCollection 2025 Jun.
BACKGROUND
This study aimed to evaluate the efficacy and safety of adjuvant pembrolizumab in patients with completely resected stage I lung adenocarcinoma with micropapillary or solid-pattern (MPSOL).
METHODS
This was a single-center, single-arm phase 2 study (ClinicalTrials.gov identifier: NCT03254004). Key eligibility criteria included patients with stage I lung adenocarcinoma (per the American Joint Committee on Cancer 8th edition; primary tumor of <4 cm and without nodal metastasis), characterized by MPSOL histological subtype upon postsurgical pathological examination Patients were treated with pembrolizumab 200 mg every 3 weeks for 1 year or until disease recurrence or intolerable toxicity. The primary endpoint was 3-year disease-free survival (DFS), defined as the time from surgery to recurrence or death from any cause. Secondary endpoints included overall survival and safety.
FINDINGS
Between September 17, 2018, and February 10, 2022, 70 patients were enrolled. At a median follow-up of 45·0 months, the 3-year disease-free survival (DFS) was 83·2%, meeting the survival endpoint of >80%. Patients with mutations showed significantly poorer DFS than those with wild-type (hazard ratio [HR]: 5·01 [95% confidence interval (CI): 1·11-22·70], = 0·036), although no significant differences were noted according to age, smoking status, tumor size, and PD-L1 tumor proportion score. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 6 patients (8·6%). Thirteen AEs led to treatment discontinuation and the majority of these AEs resolved upon discontinuation and subsequent steroid treatment.
INTERPRETATION
Adjuvant pembrolizumab exhibited promising clinical efficacy in patients with stage I lung MPSOL, particularly those with EGFR-wild type, and exhibited tolerable safety.
FUNDING
Merk Sharp & Dohme (MSD). The funders had no role in study design, data collection, data analysis, interpretation, or writing of the report.
背景
本研究旨在评估辅助帕博利珠单抗治疗完全切除的I期微乳头或实性模式（MPSOL）肺腺癌患者的疗效和安全性。
方法
这是一项单中心、单臂2期研究（ClinicalTrials.gov标识符：NCT03254004）。主要入选标准包括I期肺腺癌患者（根据美国癌症联合委员会第8版；原发肿瘤<4 cm且无淋巴结转移），术后病理检查显示为MPSOL组织学亚型。患者每3周接受200 mg帕博利珠单抗治疗，持续1年，或直至疾病复发或出现无法耐受的毒性。主要终点为3年无病生存期（DFS），定义为从手术到复发或因任何原因死亡的时间。次要终点包括总生存期和安全性。
结果
2018年9月17日至2022年2月10日期间，共纳入70例患者。中位随访45.0个月时，3年无病生存期（DFS）为83.2%，达到了>80%的生存终点。有 突变的患者DFS显著低于 野生型患者（风险比[HR]：5.01[95%置信区间（CI）：1.11 - 22.70]，P = 0.036），不过在年龄、吸烟状态、肿瘤大小和PD-L1肿瘤比例评分方面未观察到显著差异。6例患者（8.6%）发生3级或4级治疗相关不良事件（AE）。13例AE导致治疗中断，大多数AE在中断治疗及随后的类固醇治疗后得到缓解。
解读
辅助帕博利珠单抗在I期MPSOL肺腺癌患者中显示出有前景的临床疗效，尤其是EGFR野生型患者，并显示出可耐受的安全性。
资助
默克雪兰诺（MSD）。资助者在研究设计、数据收集、数据分析、解读或报告撰写方面没有参与。
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