Research in context
Evidence before this study
We searched PubMed for reports of clinical trials published within the past 5 years using the terms “squamous cell carcinoma”, “head and neck”, and “metastatic”. We reviewed abstracts to identify trials of platinum-pretreated disease and specifically any studies that investigated phosphatidylinositol 3-kinase (PI3K) inhibitors in this setting. Although many agents and treatment combinations have been evaluated in this setting, no present second-line therapy options for squamous cell carcinoma of the head and neck are based on phase 3 trial results. Of note, few studies that specifically investigated PI3K inhibitors in squamous cell carcinoma of the head and neck were identified, despite laboratory data suggesting a role for PI3K inhibition in squamous cell carcinoma of the head and neck.
Added value of this study
Our results show that use of buparlisib, a novel, oral pan-PI3K inhibitor, in combination with paclitaxel produced clinically meaningful improvements in progression-free survival, overall survival, and the proportion of patients with an overall response compared with paclitaxel alone in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck. To our knowledge, these results provide the first clinical data to show a role for PI3K inhibition specifically in squamous cell carcinoma of the head and neck. Of note, this study achieved a nearly three-times increase in the proportion of patients with an overall response with buparlisib compared with placebo. Additionally, to our knowledge, this study recorded the longest median overall survival reported so far in the second-line setting, which compares favourably with the overall survival reported with existing first-line standard-of-care treatment (ie, cetuximab, platinum, or fluorouracil triplet).
Implications of all the available evidence
On the basis of the improved clinical efficacy with a manageable safety profile, our findings suggest that buparlisib in combination with paclitaxel could become an important second-line treatment option for patients with recurrent or metastatic squamous cell carcinoma of the head and neck eligible for taxane therapy. Further phase 3 studies are warranted to confirm this phase 2 finding.