D Ross Camidge1, Aliyah Pabani2, Ronni M Miller3, Naiyer A Rizvi2, Lyudmila Bazhenova4. 1. University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, Colorado. Electronic address: Ross.camidge@ucdenver.edu. 2. Columbia University Medical Center, Division of Hematology and Oncology, New York, New York. 3. University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, Colorado. 4. University of California San Diego, Moores Cancer Center, La Jolla, California.
Abstract
INTRODUCTION: Rare cases of early-onset pulmonary events (EOPEs) occurring within days of the start of administration of brigatinib have been reported (incidence 3%-6% with use of the recommended dose of 90 mg for 7 days and then a 180-mg step-up dosing regimen). Current prescribing information suggests dose interruption and then dose reduction for grade 1 or 2 events and discontinuation for recurrent or higher grade events. However, clinical experience suggests that alternative strategies exist to safely maintain dosing. METHODS: Case vignettes illustrating different EOPE clinical scenarios were assembled; they included (1) successful treatment through the initial EOPE, (2) successful rechallenge after the EOPE, (3) successful rechallenge after the EOPE with utilization of a shallower step-up regimen, and (4) unsuccessful rechallenge. RESULTS: Rapid tolerization to EOPEs within 5 to 8 days may occur with continued dosing, suggesting that dose interruption could be avoided with close observation and temporary supportive care (including supplemental oxygen). If dose interruption occurs, restarting administration of brigatinib at 30 mg, followed by dose increases in 30-mg increments every 3 days to the full dose as tolerated ("shallow step-up dosing") may maximize safety during rechallenge. As compromised baseline respiratory function may increase the rate of clinically apparent EOPEs, proactive use of shallow step-up dosing could be considered in select cases. CONCLUSIONS: Clinically apparent EOPEs are a rare complication of brigatinib. They occur within days of starting administration of the drug, with rapid tolerization possible during continued dosing. Adapting the EOPE nomenclature to include the word transient (TEOPE) may further clinician and patient understanding in distinguishing these events from the pneumonitis seen with other tyrosine kinase inhibitors. Improved education and appropriate supportive care and dosing should allow more patients to maximally and safely benefit from brigatinib.
INTRODUCTION: Rare cases of early-onset pulmonary events (EOPEs) occurring within days of the start of administration of brigatinib have been reported (incidence 3%-6% with use of the recommended dose of 90 mg for 7 days and then a 180-mg step-up dosing regimen). Current prescribing information suggests dose interruption and then dose reduction for grade 1 or 2 events and discontinuation for recurrent or higher grade events. However, clinical experience suggests that alternative strategies exist to safely maintain dosing. METHODS: Case vignettes illustrating different EOPE clinical scenarios were assembled; they included (1) successful treatment through the initial EOPE, (2) successful rechallenge after the EOPE, (3) successful rechallenge after the EOPE with utilization of a shallower step-up regimen, and (4) unsuccessful rechallenge. RESULTS: Rapid tolerization to EOPEs within 5 to 8 days may occur with continued dosing, suggesting that dose interruption could be avoided with close observation and temporary supportive care (including supplemental oxygen). If dose interruption occurs, restarting administration of brigatinib at 30 mg, followed by dose increases in 30-mg increments every 3 days to the full dose as tolerated ("shallow step-up dosing") may maximize safety during rechallenge. As compromised baseline respiratory function may increase the rate of clinically apparent EOPEs, proactive use of shallow step-up dosing could be considered in select cases. CONCLUSIONS: Clinically apparent EOPEs are a rare complication of brigatinib. They occur within days of starting administration of the drug, with rapid tolerization possible during continued dosing. Adapting the EOPE nomenclature to include the word transient (TEOPE) may further clinician and patient understanding in distinguishing these events from the pneumonitis seen with other tyrosine kinase inhibitors. Improved education and appropriate supportive care and dosing should allow more patients to maximally and safely benefit from brigatinib.
Authors: Terry L Ng; Amber Johnson; Raphael A Nemenoff; Elena Hsieh; Andrea Abeyta Osypuk; Adrie van Bokhoven; Howard Li; D Ross Camidge; Erin L Schenk Journal: J Thorac Oncol Date: 2020-12-09 Impact factor: 15.609
Authors: Ke Wang; Juan Li; Jianguo Sun; Li Li; Xi Zhang; Jianyong Zhang; Min Yu; Xianwei Ye; Ming Zhang; Yu Zhang; Wenxiu Yao; Meijuan Huang Journal: Zhongguo Fei Ai Za Zhi Date: 2021-10-21
Authors: D Ross Camidge; Hye Ryun Kim; Myung-Ju Ahn; James C H Yang; Ji-Youn Han; Maximilian J Hochmair; Ki Hyeong Lee; Angelo Delmonte; Maria Rosario García Campelo; Dong-Wan Kim; Frank Griesinger; Enriqueta Felip; Raffaele Califano; Alexander Spira; Scott N Gettinger; Marcello Tiseo; Huamao M Lin; Neeraj Gupta; Michael J Hanley; Quanhong Ni; Pingkuan Zhang; Sanjay Popat Journal: J Clin Oncol Date: 2020-08-11 Impact factor: 44.544