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

Summary Background Phosphatidylinositol 3-kinase (PI3K) pathway activation in squamous cell carcinoma of the head and neck contributes to treatment resistance and disease progression. Buparlisib, a pan-PI3K inhibitor, has shown preclinical antitumour activity and objective responses in patients with...

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Published in:The lancet oncology 2017-03, Vol.18 (3), p.323-335
Main Authors: Soulières, Denis, Prof, Faivre, Sandrine, Prof, Mesía, Ricard, Prof, Remenár, Éva, Prof, Li, Shau-Hsuan, Prof, Karpenko, Andrey, Prof, Dechaphunkul, Arunee, MD, Ochsenreither, Sebastian, Prof, Kiss, Laura Anna, Prof, Lin, Jin-Ching, Prof, Nagarkar, Raj, Prof, Tamás, László, Prof, Kim, Sung-Bae, Prof, Erfán, Jozsef, Prof, Alyasova, Anna, Prof, Kasper, Stefan, Prof, Barone, Carlo, Prof, Turri, Sabine, MS, Chakravartty, Arunava, PhD, Chol, Marie, PhD, Aimone, Paola, Prof, Hirawat, Samit, Prof, Licitra, Lisa, Prof
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Adult
Aged
Aged, 80 and over
Aminopyridines - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Automation
Cancer
Cancer therapies
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - secondary
Cell activation
Chemotherapy
Clinical trials
Disease resistance
Double-Blind Method
Double-blind studies
Female
Follow-Up Studies
Head
Head & neck cancer
Head and Neck Neoplasms - drug therapy
Head and Neck Neoplasms - pathology
Hematology, Oncology and Palliative Medicine
Humans
Hyperglycemia
International Agencies
Intravenous administration
Kinases
Laboratories
Male
Medical prognosis
Metastases
Metastasis
Middle Aged
Morpholines - administration & dosage
Neck
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - pathology
Neoplasm Staging
Neutropenia
Paclitaxel
Paclitaxel - administration & dosage
Patients
Platinum
Platinum - administration & dosage
Prognosis
Safety
Solid tumors
Squamous cell carcinoma
Studies
Survival analysis
Survival Rate
Tumors
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Summary:Summary Background Phosphatidylinositol 3-kinase (PI3K) pathway activation in squamous cell carcinoma of the head and neck contributes to treatment resistance and disease progression. Buparlisib, a pan-PI3K inhibitor, has shown preclinical antitumour activity and objective responses in patients with epithelial malignancies. We assessed whether the addition of buparlisib to paclitaxel improves clinical outcomes compared with paclitaxel and placebo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Methods In this multicentre, randomised, double-blind, placebo-controlled phase 2 study (BERIL-1), we recruited patients aged 18 years and older with histologically or cytologically confirmed recurrent and metastatic squamous cell carcinoma of the head and neck after disease progression on or after one previous platinum-based chemotherapy regimen in the metastatic setting. Eligible patients were enrolled from 58 centres across 18 countries and randomly assigned (1:1) to receive second-line oral buparlisib (100 mg once daily) or placebo, plus intravenous paclitaxel (80 mg/m2 on days 1, 8, 15, and 22) in 28 day treatment cycles. Randomisation was done via a central patient screening and randomisation system with an interactive (voice and web) response system and stratification by number of previous lines of therapy in the recurrent and metastatic setting and study site. Patients and investigators (including local radiologists) were masked to treatment assignment from randomisation until the final overall survival analysis. The primary endpoint was progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in all randomly assigned patients. Efficacy analyses were done on the intention-to-treat population, whereas safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received. This trial is registered with ClinicalTrials.gov , number NCT01852292 , and is ongoing but no longer enrolling patients. Findings Between Nov 5, 2013, and May 5, 2015, 158 patients were enrolled and randomly assigned to receive either buparlisib plus paclitaxel (n=79) or placebo plus paclitaxel (n=79). Median progression-free survival was 4·6 months (95% CI 3·5–5·3) in the buparlisib group and 3·5 months (2·2–3·7) in the placebo group (hazard ratio 0·65 [95% CI 0·45–0·95], nominal one-sid
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(17)30064-5