The addition of buparlisib to second-line paclitaxel improved progression-free survival compared with paclitaxel alone among patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC), according to a study published in The Lancet Oncology.1
Previous studies demonstrated that phosphatidylinositol 3-kinase (PI3K) pathway activation plays a role in treatment resistance and disease progression in HSNCC. The pan-PI3K inhibitor, buparlisib, exhibited antitumor activity in preclinical models and resulted in objective responses among patients with epithelial malignancies.
For this study, investigators evaluated whether adding buparlisib to paclitaxel improves clinical outcomes vs paclitaxel and placebo among patients with recurrent or metastatic HSNCC.
For the multicenter, double-blind, phase 2 BERIL-1 trial (ClinicalTrials.gov Identifier: NCT01852292), investigators enrolled 158 patients with histologically or cytologically confirmed recurrent and metastatic HSNCC who experienced disease progression on or after 1 previous platinum-based chemotherapy regimen.
Treatment with buparlisib significantly reduced the risk of progression or death by 35% compared with paclitaxel alone (hazard ratio, 0.65; 95% CI, 0.45-0.95; P = .011). Median progression-free survival was 4.6 months (95% CI, 3.5-5.3) in the combination arm vs 3.5 months (95% CI, 2.2-3.7) in the placebo arm.
The most frequent grade 3 to 4 adverse events in the buparlisib group were hyperglycemia, anemia, neutropenia, and fatigue. Fifty-seven percent of patients in the buparlisib arm reported serious adverse events compared with 47% in the placebo arm. No deaths were considered treatment-related.
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The findings suggest that buparlisib plus paclitaxel could be an effective strategy for the second-line treatment of patients with platinum-pretreated recurrent or metastatic HNSCC. Phase 3 clinical trials are warranted to confirm the results of this study.
- Soulieres D, Faivre S, Mesia R, et al. Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Oncol. 2017 Jan 25. doi: 10.1016/S1470-2045(17)30064-5 [Epub ahead of print]