Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012

Br J Cancer. 2018 Jul;119(2):153-159. doi: 10.1038/s41416-018-0131-9. Epub 2018 Jun 29.


Background: Second-line treatment options for advanced head and neck squamous cell carcinoma (HNSCC) are limited. The phase Ib KEYNOTE-012 study evaluated the safety and the efficacy of pembrolizumab for the treatment of HNSCC after long-term follow-up.

Methods: Multi-centre, non-randomised trial included two HNSCC cohorts (initial and expansion) in which 192 patients were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks (initial cohort; N = 60) or 200 mg every 3 weeks (expansion cohort; N = 132). Co-primary endpoints were safety and overall response rate (ORR; RECIST v1.1; central imaging vendor review).

Results: Median follow-up was 9 months (range, 0.2-32). Treatment-related adverse events (AEs) of any grade and grade 3/4 occurred in 123 (64%) and 24 (13%) patients, respectively. No deaths were attributed to treatment-related AEs. ORR was 18% (34/192; 95% CI, 13-24%). Median response duration was not reached (range, 2+ to 30+ months); 85% of responses lasted ≥6 months. Overall survival at 12 months was 38%.

Conclusions: Some patients received 2 years of treatment and the responses were ongoing for more than 30 months; the durable anti-tumour activity and tolerable safety profile, observed with long-term follow-up, support the use of pembrolizumab as a treatment for recurrent/metastatic HNSCC.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • B7-H1 Antigen / genetics
  • Drug-Related Side Effects and Adverse Reactions / classification
  • Drug-Related Side Effects and Adverse Reactions / pathology*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Progression-Free Survival
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / pathology


  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • CD274 protein, human
  • pembrolizumab