In the phase II BERIL-1 trial reported in The Lancet Oncology, Soulières et al found that adding the pan-PI3K (phosphatidylinositol 3-kinase) inhibitor buparlisib to paclitaxel improved outcomes in patients with platinum-pretreated recurrent metastatic squamous cell carcinoma of the head and neck. Lisa Licitra, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori, is the corresponding author of The Lancet Oncology article.
In the double-blind trial, 158 patients from 58 sites in 18 countries were randomized between November 2013 and May 2015 to receive buparlisib at 100 mg once daily plus paclitaxel at 80 mg/m2 on days 1, 8, 15, and 22 (n = 79) or placebo plus paclitaxel (n = 79) in 28-day cycles. Patients had to have disease progression on or after one previous platinum-based regimen in the metastatic setting. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population.
Outcomes and Toxicity
Median duration of follow-up was 18.1 months. Median progression-free survival was 4.6 months (95% confidence interval [CI] = 3.5–5.3 months) in the buparlisib group vs 3.5 months (95% CI = 2.2–3.7 months) in the placebo group (hazard ratio [HR] = 0.65, P = .011). Median overall survival was 10.4 months vs 6.5 months (HR = 0.72, P = .041). Additional therapy was received after disease progression in 28% vs 32% of patients. Overall response rates were 39% vs 14% (P = .00031).
Grade 3 or 4 adverse events occurred in 82% of the buparlisib group and 72% of the placebo group, with the most common in the buparlisib group being hyperglycemia (22% vs 3%), anemia (18% vs 12%), neutropenia (17% vs 5%), fatigue (8% vs 10%), and asthenia (8% vs 4%). Serious adverse events occurred in 57% vs 47%. Treatment was discontinued due to adverse events in 10% vs 14%. On-treatment death occurred in 20% vs 22%, with no deaths considered related to study treatment.
The investigators concluded: “On the basis of the improved clinical efficacy with a manageable safety profile, the results of this randomised phase 2 study suggest that buparlisib in combination with paclitaxel could be an effective second-line treatment for patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck. Further phase 3 studies are warranted to confirm this phase 2 finding.”
The study was funded by Novartis Pharmaceuticals Corporation. ■