The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis

Cancer Immunol Immunother. 2024 May 11;73(7):125. doi: 10.1007/s00262-024-03698-2.

Abstract

Background: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC <induction chemotherapy> plus cisplatin CCRT <concurrent chemoradiotherapy>) for LANPC patients.

Methods: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors.

Results: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064).

Conclusion: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Keywords: Efficacy; Induction chemotherapy; Nasopharyngeal carcinoma; PD-1 blockade; Toxicity.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Chemoradiotherapy* / methods
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • Gemcitabine
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Induction Chemotherapy* / methods
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma* / drug therapy
  • Nasopharyngeal Carcinoma* / mortality
  • Nasopharyngeal Carcinoma* / therapy
  • Nasopharyngeal Neoplasms* / drug therapy
  • Nasopharyngeal Neoplasms* / mortality
  • Nasopharyngeal Neoplasms* / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Propensity Score*
  • Retrospective Studies

Substances

  • Programmed Cell Death 1 Receptor
  • Immune Checkpoint Inhibitors
  • Cisplatin
  • Deoxycytidine
  • Gemcitabine