A pilot study of the pan-class I PI3K inhibitor buparlisib in combination with cetuximab in patients with recurrent/metastatic head and neck cancer.

Abstract

6039 Background: R/M HNC carries a poor prognosis with a median survival of 10-12 months. PI3K pathway aberrations are present in 30% of HNC. This pilot dose-escalation study assesses the safety and tolerability of the PI3K inhibitor buparlisib when given concurrently with cetuximab in R/M HNC, as well as assess efficacy in an expansion cohort. Methods: Patients (pts) with R/M HNC who were not amenable to curative intent therapy were enrolled. Pts were given oral buparlisib starting day -7 and daily thereafter. The dose of buparlisib was escalated in a 3+3 design (Level 1: 80mg daily, Level 2: 100 mg daily) followed by a dose expansion cohort. The maximum dose of buparlisib was 100 mg daily. Cetuximab (500mg/m2) was given intravenously every 14 days starting day 0. Pts continued on treatment until progression of disease. Prior cetuximab failure was allowed. Results: Of the 12 pts enrolled, 10 had at least 2 previous treatment regimens (11 with prior cetuximab). 5 pts were HPV+, 4 were HPV-, and 3 had unknown HPV status. 3 pts were treated at the 80 mg dose level while 9 were treated at the 100 mg dose level (3 + 6 patient expansion). Treatment was well tolerated with 2 pts experiencing grade 3 adverse events (AEs) (no grade 4 AEs). The most common AEs were fatigue (83.3%), maculopapular rash (50.0%), and anorexia (50.0%). 3 pts experienced grade 1 anxiety. There were no SAEs. Of the 10 pts who were evaluable for response one patient achieved a PR (10%), and 4 achieved stable disease (40%) per RECIST 1.1. Median overall survival was 280 days (HPV+: 370 days, HPV-:191 days). The study was closed early due to poor enrollment on the expansion cohort as patients opted for concurrently open immunotherapy trials. Conclusions: Based on this pilot study, buparlisib plus cetuximab proved to be well-tolerated and showed limited evidence of activity in a heavily pre-treated patient population. Further research is warranted to determine activity of buparlisib in a larger cohort of R/M HNC. Clinical trial information: NCT01816984.