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

Hye Ryun Kim, Han Na Kang, Mi Ran Yun, Kwon Young Ju, Jae Woo Choi, Dong Min Jung, Kyoung Ho Pyo, Min Hee Hong, Myoung Ju Ahn, Jong Mu Sun, Han Sang Kim, Jinna Kim, Jinseon Yoo, Kyu Ryung Kim, Yoon Woo Koh, Se Heon Kim, Eun Chang Choi, Sun Ock Yoon, Hyo Sup Shim, Soonmyung PaikTae Min Kim, Byoung Chul Cho

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Abstract

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.

Original languageEnglish
Pages (from-to)1720-1729
Number of pages10
JournalBritish journal of cancer
Volume123
Issue number12
DOIs
Publication statusPublished - 2020 Dec 8

Bibliographical note

Funding Information:
Funding information This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Basic Science Research Programme through the NRF funded by the Ministry of Science and ICT (2016R1A2B3016282 to B.C.C.) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (HI13C2162 to S.P.).

Publisher Copyright:
© 2020, The Author(s).

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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