An evaluation of buparlisib for the treatment of head and neck squamous cell carcinoma

ABSTRACT

Introduction

Five-year overall survival for head and neck squamous cell carcinoma (HNSCC) is relatively poor at around 50–66%, and there has been little improvement over the past several decades. PIK3CA alterations are common in HNSCC and offer a promising therapeutic target.

Areas covered

The authors discuss the PIK3 pathway and the use of PIK3 inhibitors in cancer, with a particular focus on HNSCC. A summary of the safety and efficacy of buparlisib, a class I pan-PI3K inhibitor, from several phase I and phase II HNSCC trials is provided.

Expert opinion

With a maximum tolerated dose of 100 mg/day and an acceptable toxicity profile, buparlisib may be effective in HNSCC, irrespective of PIK3CA mutational status. On-going clinical trials will help determine the developmental strategy of buparlisib while novel combinatory strategies including combination with immune checkpoint inhibitors should be considered. Importantly, biomarker strategies, including wider use of tumor sequencing and circulating tumor DNA, should be utilized to improve patient selection.

KEYWORDS:

• Head and neck neoplasms
• buparlisiib
• pi3k
• precision medicine

Article highlight

• PIK3CA alterations are commonly identified in head and neck squamous cell carcinoma (HNSCC), however no PIK3 therapies are currently approved for use.

• Buparlisib is a class I pan-PI3K inhibitor targeting the ATP binding site in the kinase domain of all four p110 isoforms.

• Multiple early phase studies have evaluated the safety and efficacy of buparlisib in HNSCC.

• The combination of buparlisib and paclitaxel may be efficacious in recurrent/metastatic HNSCC. A randomized Phase 3 clinical trial evaluating this combination is on-going.

• A need exists for the use of PIK3 inhibition in HNSCC, however further studies are needed to identify the optimal PIK3 agent, combinational strategy, and line of treatment.

This Box summaries key points contained in the article.

Acknowledgments

The authors thank Kristian Figueras MD for his assistance with data collection.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer declares having direct involvement with the Phase II buparlisib trial and will also have involvement with the phase III trial while another reviewer is part of the steering committee of the phase III trial in HNSCC with buparlisib. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.