Mouse–human co-clinical trials demonstrate superior anti-tumour effects of buparlisib (BKM120) and cetuximab combination in squamous cell carcinoma of head and neck
-
Published:2020-09-23
Issue:12
Volume:123
Page:1720-1729
-
ISSN:0007-0920
-
Container-title:British Journal of Cancer
-
language:en
-
Short-container-title:Br J Cancer
Author:
Kim Hye Ryun, Kang Han Na, Yun Mi Ran, Ju Kwon Young, Choi Jae Woo, Jung Dong Min, Pyo Kyoung Ho, Hong Min Hee, Ahn Myoung-Ju, Sun Jong-Mu, Kim Han Sang, Kim Jinna, Yoo Jinseon, Kim Kyu Ryung, Koh Yoon Woo, Kim Se Heon, Choi Eun Chang, Yoon Sun Ock, Shim Hyo SupORCID, Paik Soonmyung, Kim Tae-Min, Cho Byoung ChulORCID
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
Reference32 articles.
1. Hunter, K. D., Parkinson, E. K. & Harrison, P. R. Profiling early head and neck cancer. Nat. Rev. Cancer 5, 127–135 (2005). 2. Lim, S. M., Cho, S. H., Hwang, I. G., Choi, J. W., Chang, H., Ahn, M. J. et al. Investigating the feasibility of targeted next-generation sequencing to guide the treatment of head and neck squamous cell carcinoma. Cancer Res. Treat. 51, 300–312 (2019). 3. Vermorken, J. B., Trigo, J., Hitt, R., Koralewski, P., Diaz-Rubio, E., Rolland, F. et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J. Clin. Oncol. 25, 2171–2177 (2007). 4. Cohen, E. E. W., Soulieres, D., Le Tourneau, C., Dinis, J., Licitra, L., Ahn, M. J. et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 393, 156–167 (2019). 5. Ferris, R. L., Blumenschein, G. Jr., Fayette, J., Guigay, J., Colevas, A. D., Licitra, L. et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 375, 1856–1867 (2016).
Cited by
22 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|