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

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. Funding: Merk Sharp & Dohme (MSD). The funders had no role in study design, data collection, data analysis, interpretation, or writing of the report.