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).
Bibliographic record
Abstract
6008 Background: The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in HNSCC, contributing to treatment resistance and disease progression. Buparlisib (BUP) is a pan-PI3K inhibitor that elicits tumor control in preclinical models of HNSCC and shows signs of clinical activity in other squamous cancers. Methods: In this phase II study (NCT01852292), patients (pts) with recurrent/metastatic HNSCC progressing after platinum-based therapy were randomized (1:1) to receive BUP (100 mg/day) + paclitaxel (PAC; 80 mg/m2/week) or placebo (PBO) + PAC, stratified by prior lines of treatment (1 vs 2) and study site (North America vs rest of world), until progressive disease (PD) or discontinuation. The primary endpoint was progression-free survival (PFS; per RECIST v1.1). Overall survival (OS) was the key secondary endpoint; other secondary endpoints included overall response rate (ORR) and safety (per CTCAE v4.03). 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 (HPV)-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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".