Adjuvant pembrolizumab therapy for completely resected stage I lung adenocarcinoma with micropapillary or solid histological subtypes: a single-center, single-arm, phase 2 trial

초록

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 EGFR mutations showed significantly poorer DFS than those with EGFR wild-type (hazard ratio [HR]: 5.01 [95% confidence interval (CI): 1.11-22.70], P = 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. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

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