Head and Neck Cancer
ASCO 2016. Abstract 6008. BERIL-1: A phase II, placebo-controlled study of buparlisib (BKM120) plus paclitaxel in patients with platinum-pretreated recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
Denis Soulières et al.
Results: As of August 31, 2015, 158 pts were randomized to receive BUP + PAC vs PBO + PAC (n = 79 each), with 10 (13%) and 7 (9%) pts ongoing, respectively. Median age was 59 vs 58 years; 29% vs 39% of pts had laryngeal/hypopharyngeal primary tumors; 67% vs 79% were human papillomavirus (`)-negative; and 52% vs 38% had received a prior EGFR inhibitor. Primary reasons for treatment discontinuation were PD in 46% vs 60% of pts, and adverse events (AEs) in 9% vs 14%. Median PFS was improved for BUP vs PBO (4.6 vs 3.5 months; hazard ratio [HR] 0.65 [95% CI: 0.45–0.95]). Posterior probability of (HR < 1) was > 97.5%. The PFS improvement was consistent across exploratory subgroups. ORR was 39% vs 14%. Median OS at data cut-off was 10.0 vs 6.5 months (HR 0.71 [95% CI: 0.46–1.1]), based on 84/112 (75%) planned deaths. Grade 3/4 AEs ( ≥ 10% of pts) were hyperglycemia (22% vs 3%), anemia (18% vs 12%), neutropenia (17% vs 5%), and fatigue (8% vs 10%).
Conclusions: The BERIL-1 study met its primary endpoint, demonstrating improved PFS for the combination of BUP + PAC vs PAC, notably in pts with poor prognosis HNSCC (73% of pts were HPV-negative). The safety profile of the combination was manageable. Follow-up for final OS analysis is ongoing. Clinical trial information:NCT01852292
CARE™ Faculty Perspective: The combination of buparlisib with paclitaxel is superior to taxanes. While a greater advantage was seen with HPV negative patients, some benefit was derived for HPV positive patients as well. We await the overall survival data.