Ryan J Brisson1, Sara Kochanny2, Saba Arshad3, Allison Dekker2, Jonas A DeSouza4, Vassiliki Saloura5, Everett E Vokes2,6, Tanguy Y Seiwert2,6. 1. Oakland University William Beaumont School of Medicine, Rochester, Michigan. 2. Department of Medicine, The University of Chicago Medicine, Chicago, Illinois. 3. Department of Medicine, Blake Medical Center, Bradenton, Florida. 4. Humana, Louisville, Kentucky. 5. National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 6. The University of Chicago Comprehensive Cancer Center, Chicago, Illinois.
Abstract
BACKGROUND: This study assessed the maximum tolerated dose (MTD) of the PI3K inhibitor buparlisib given concurrently with cetuximab in recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). METHODS: Twelve patients with R/M HNSCC were enrolled. Patients were given oral buparlisib starting day 7 and daily thereafter. The dose of buparlisib was escalated in a 3 + 3 design followed by a dose expansion cohort of 6 patients. The MTD of buparlisib per protocol was 100 mg daily with cetuximab given intravenously every 14 days starting day 0. RESULTS: Ten patients had ≥2 previous treatment regimens (11 with prior cetuximab). There were no dose limiting toxicities observed during dose escalation. One patient achieved a partial response and 4 achieved stable disease. CONCLUSION: Based on this pilot study, buparlisib at 100 mg daily plus cetuximab proved to be well-tolerated. Patients previously treated with cetuximab monotherapy showed benefit from this combination.
BACKGROUND: This study assessed the maximum tolerated dose (MTD) of the PI3K inhibitor buparlisib given concurrently with cetuximab in recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). METHODS: Twelve patients with R/M HNSCC were enrolled. Patients were given oral buparlisib starting day 7 and daily thereafter. The dose of buparlisib was escalated in a 3 + 3 design followed by a dose expansion cohort of 6 patients. The MTD of buparlisib per protocol was 100 mg daily with cetuximab given intravenously every 14 days starting day 0. RESULTS: Ten patients had ≥2 previous treatment regimens (11 with prior cetuximab). There were no dose limiting toxicities observed during dose escalation. One patient achieved a partial response and 4 achieved stable disease. CONCLUSION: Based on this pilot study, buparlisib at 100 mg daily plus cetuximab proved to be well-tolerated. Patients previously treated with cetuximab monotherapy showed benefit from this combination.
Authors: Johanna C Bendell; Jordi Rodon; Howard A Burris; Maja de Jonge; Jaap Verweij; Diana Birle; David Demanse; Stefan S De Buck; Qinhua C Ru; Malte Peters; Michael Goldbrunner; José Baselga Journal: J Clin Oncol Date: 2011-12-12 Impact factor: 44.544
Authors: Søren M Bentzen; Beste M Atasoy; Frances M Daley; Stanley Dische; Paul I Richman; Michele I Saunders; Klaus R Trott; George D Wilson Journal: J Clin Oncol Date: 2005-08-20 Impact factor: 44.544
Authors: Tanguy Y Seiwert; Barbara Burtness; Ranee Mehra; Jared Weiss; Raanan Berger; Joseph Paul Eder; Karl Heath; Terrill McClanahan; Jared Lunceford; Christine Gause; Jonathan D Cheng; Laura Q Chow Journal: Lancet Oncol Date: 2016-05-27 Impact factor: 41.316
Authors: Angelo Di Leo; Stephen Johnston; Keun Seok Lee; Eva Ciruelos; Per E Lønning; Wolfgang Janni; Ruth O'Regan; Marie-Ange Mouret-Reynier; Dimitar Kalev; Daniel Egle; Tibor Csőszi; Roberto Bordonaro; Thomas Decker; Vivianne C G Tjan-Heijnen; Sibel Blau; Alessio Schirone; Denis Weber; Mona El-Hashimy; Bharani Dharan; Dalila Sellami; Thomas Bachelot Journal: Lancet Oncol Date: 2017-12-07 Impact factor: 41.316
Authors: Sarah Wheeler; Doris R Siwak; Raymond Chai; Courtney LaValle; Raja R Seethala; Lin Wang; Kathleen Cieply; Carol Sherer; Corwin Joy; Gordon B Mills; Athanassios Argiris; Jill M Siegfried; Jennifer R Grandis; Ann Marie Egloff Journal: Clin Cancer Res Date: 2012-02-20 Impact factor: 12.531
Authors: Robert L Ferris; George Blumenschein; Jerome Fayette; Joel Guigay; A Dimitrios Colevas; Lisa Licitra; Kevin Harrington; Stefan Kasper; Everett E Vokes; Caroline Even; Francis Worden; Nabil F Saba; Lara C Iglesias Docampo; Robert Haddad; Tamara Rordorf; Naomi Kiyota; Makoto Tahara; Manish Monga; Mark Lynch; William J Geese; Justin Kopit; James W Shaw; Maura L Gillison Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245
Authors: Khoa A Nguyen; Madison J Keith; Stephen B Keysar; Spencer C Hall; Anamol Bimali; Antonio Jimeno; Xiao-Jing Wang; Christian D Young Journal: Mol Carcinog Date: 2022-04-13 Impact factor: 5.139
Authors: Michelle J Lee; Nan Jin; Jennifer R Grandis; Daniel E Johnson Journal: Biochim Biophys Acta Mol Cell Res Date: 2020-02-19 Impact factor: 4.739