Perioperative Pembrolizumab for Locally Advanced Thymic Epithelial Tumors: A Single-Arm, Phase 2 Trial

J Thorac Oncol. 2025 Dec;20(12):1829-1842. doi: 10.1016/j.jtho.2025.08.011. Epub 2025 Oct 19.

Abstract

Introduction: Complete surgical resection remains the only potentially curative option for thymic epithelial tumors (TETs). We hypothesized that adding perioperative pembrolizumab to standard therapy may improve response, resectability, and disease-free survival (DFS).

Methods: In this single-arm, prospective phase 2 trial, patients with potentially resectable TETs (Masaoka-Koga stages III-IV) received neoadjuvant docetaxel (75 mg/m2), cisplatin (75 mg/m2), and pembrolizumab (200 mg) every 3 weeks for 3 cycles, followed by surgery and maintenance pembrolizumab for 2 years. R1/R2-resected patients received adjuvant radiotherapy concomitant with pembrolizumab. The primary end point was a major pathologic response (MPR).

Results: From March 2020 to January 2025, 40 untreated patients were recruited, including those with WHO B3 thymoma (n = 7, 17.5%) or thymic carcinoma (n = 29, 72.5%). Most were diagnosed with stage IV disease (n = 31, 77.5%). The median follow-up duration was 27.5 months (95% confidence interval [CI]: 22.0-39.2), and 28 patients (70.0%) underwent surgical resection. Among the patients who received surgery, MPR and pathologic complete response were observed in 13 (46.4%) and five (17.9%) patients, respectively. Notably, all cases of MPR and pathologic complete response occurred exclusively in patients with thymic carcinoma, not in those with thymoma. The 1-year DFS rate was 91.0% (95% CI: 79.9-100.0), and the median DFS was 49.3 months (95% CI: 25.3-not reached) from the time point of surgery. Most of the adverse events were grade 1 or 2 (n = 21, 52.5%), with nine (22.5%) grade 3 and five (12.5%) grade 4. Two patients with thymoma died from myocarditis.

Conclusions: Perioperative pembrolizumab demonstrated promising rates of MPR, R0 resection, and long-term DFS in stage III to IV TETs.

Clinical trial registration: NCT03858582 (MK3475-971).

Keywords: Immunotherapy; Locally advanced; Perioperative treatment; Thymic epithelial tumor.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / pharmacology
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasms, Glandular and Epithelial* / drug therapy
  • Neoplasms, Glandular and Epithelial* / pathology
  • Neoplasms, Glandular and Epithelial* / surgery
  • Prospective Studies
  • Survival Rate
  • Thymus Neoplasms* / drug therapy
  • Thymus Neoplasms* / pathology
  • Thymus Neoplasms* / surgery

Substances

  • Antibodies, Monoclonal, Humanized
  • pembrolizumab

Supplementary concepts

  • Thymic epithelial tumor

Associated data

  • ClinicalTrials.gov/NCT03858582