A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer

Cancer. 2019 Sep 15;125(18):3184-3197. doi: 10.1002/cncr.32179. Epub 2019 May 31.


Background: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings.

Methods: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed.

Results: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01).

Conclusions: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

Keywords: Chemoradiation; epidermal growth factor receptor (EGFR); head and neck cancer; nimotuzumab.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Chemoradiotherapy / methods*
  • Cisplatin / therapeutic use*
  • Disease-Free Survival
  • Female
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Mucositis / etiology
  • Progression-Free Survival
  • Proportional Hazards Models
  • Squamous Cell Carcinoma of Head and Neck / therapy*
  • Survival Rate
  • Thrombocytopenia / etiology
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Antineoplastic Agents, Immunological
  • nimotuzumab
  • Cisplatin