Mouse-human co-clinical trials demonstrate superior anti-tumour effects of buparlisib (BKM120) and cetuximab combination in squamous cell carcinoma of head and neck

Br J Cancer. 2020 Dec;123(12):1720-1729. doi: 10.1038/s41416-020-01074-2. Epub 2020 Sep 23.


Background: Recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) is a common cancer with high recurrence and mortality. Current treatments have low response rates (RRs).

Methods: Fifty-three patients with R/M SCCHN received continuous oral buparlisib. In parallel, patient-derived xenografts (PDXs) were established in mice to evaluate resistance mechanisms and efficacy of buparlisib/cetuximab combination. Baseline and on-treatment tumour genomes and transcriptomes were sequenced. Based on the integrated clinical and PDX data, 11 patients with progression under buparlisib monotherapy were treated with a combination of buparlisib and cetuximab.

Results: For buparlisib monotherapy, disease control rate (DCR) was 49%, RR was 3% and median progression-free survival (PFS) and overall survival (OS) were 63 and 143 days, respectively. For combination therapy, DCR was 91%, RR was 18% and median PFS and OS were 111 and 206 days, respectively. Four PDX models were originated from patients enrolled in the current clinical trial. While buparlisib alone did not inhibit tumour growth, combination therapy achieved tumour inhibition in three of seven PDXs. Genes associated with apoptosis and cell-cycle arrest were expressed at higher levels with combination treatment than with buparlisib or cetuximab alone.

Conclusions: The buparlisib/cetuximab combination has significant promise as a treatment strategy for R/M SCCHN.

Clinical trial registration: NCT01527877.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminopyridines / adverse effects
  • Aminopyridines / therapeutic use*
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Survival / drug effects
  • Cetuximab / adverse effects
  • Cetuximab / therapeutic use*
  • DNA Copy Number Variations
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Profiling
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / mortality
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Middle Aged
  • Morpholines / adverse effects
  • Morpholines / therapeutic use*
  • Mutation
  • Neoplasm Transplantation
  • Progression-Free Survival
  • Reproducibility of Results
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Treatment Outcome
  • Up-Regulation / genetics
  • Whole Genome Sequencing / methods


  • Aminopyridines
  • Morpholines
  • NVP-BKM120
  • Cetuximab

Associated data