Neoadjuvant toripalimab plus nimotuzumab combined with taxol-based chemotherapy in locally advanced penile squamous cell carcinoma

Cancer Cell. 2025 May 12;43(5):970-980.e3. doi: 10.1016/j.ccell.2025.03.023. Epub 2025 Apr 10.

Abstract

The conventional neoadjuvant chemotherapy regimen for locally advanced penile squamous cell carcinoma (La-PSCC) has shown moderate response rates and survival benefits. This single-arm, phase II trial (NCT04475016) evaluated a neoadjuvant regimen of four cycles of toripalimab (anti-PD-1 antibody), nimotuzumab (anti-EGFR antibody), and taxol-based chemotherapy (TNT), followed by consolidative surgery. The primary endpoint was the pathological complete response (pCR) rate. Among 29 enrolled patients, 24 (82.8%) underwent consolidative surgery, with 14 (48.3%, 95% confidence interval [CI], 29.4-67.5%) achieving pCR. The objective response rate (ORR) was 82.8% (95% CI, 64.2-94.2). Median follow-up was 39.97 months, with two-year overall survival (OS) and progression-free survival (PFS) rates of 72.4% and 65.5%. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 12 (41.4%) patients, with no treatment-related deaths. Biomarker analysis identified PD-L1 expression, TP53 mutation status, and CD8+ T cell density as potential predictive markers. Therefore, neoadjuvant TNT shows promising anti-tumor activity and acceptable toxicity.

Keywords: EGFR blockade; La-PSCC; anti-PD-1 antibody; chemotherapy; neoadjuvant.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / pathology
  • Humans
  • Imidazoles / administration & dosage
  • Male
  • Middle Aged
  • Neoadjuvant Therapy* / methods
  • Paclitaxel* / administration & dosage
  • Paclitaxel* / adverse effects
  • Penile Neoplasms* / drug therapy
  • Penile Neoplasms* / genetics
  • Penile Neoplasms* / mortality
  • Penile Neoplasms* / pathology
  • Progression-Free Survival

Substances

  • Antibodies, Monoclonal, Humanized
  • Paclitaxel
  • nimotuzumab
  • toripalimab
  • Imidazoles