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Prospective Observational Study Revealing Early Pulmonary Function Changes Associated With Brigatinib Initiation
- Source :
- Journal of Thoracic Oncology. 16:486-491
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Introduction Symptomatic early onset pulmonary events (EOPEs) were observed in 3% to 6% of patients within 1 week of starting brigatinib at 90 mg daily for 7 days followed by 180 mg daily. We conducted a prospective observational cohort study to measure pulmonary function changes on initiating brigatinib. Methods Patients initiating brigatinib were eligible. Pulmonary function test (PFT) with diffusing capacity for carbon monoxide (DLCO), Borg dyspnea scale, six-minute walk test, and blood draw for cytometry by time-of-flight were performed at baseline, day 2, and day 8 plus or minus day 15 of brigatinib. The primary end point was the incidence of PFT-defined EOPEs, prespecified as greater than or equal to 20% DLCO reduction from baseline. An interim analysis was performed owing to a higher than expected incidence of DLCO reduction. Results A total of 90% (nine of 10) experienced DLCO reduction with the nadir occurring on day 2 or day 8. Median DLCO nadir was −13.33% from baseline (range: −34.44 to −5.00). Three participants met the PFT-defined EOPE criteria. All patients, including these three, were asymptomatic, none required brigatinib interruption or dose reduction, and all patients escalated to 180 mg without further issues. Despite continued dosing, by day 15, all assessed patients experienced DLCO recovery. Dyspnea and six-minute walk test results did not correlate with DLCO changes. Patients with a PFT-defined EOPE had significantly higher levels of activated neutrophils at baseline and day 8. Conclusions DLCO reduction occurred in 90% during the first 8 days of brigatinib dosing without any related symptoms. DLCO improved in all six patients assessed at day 15 despite continued dosing and dose escalation. Pretreatment levels of neutrophil activation should be explored as a biomarker for developing EOPEs.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
business.industry
Incidence (epidemiology)
respiratory system
Interim analysis
Asymptomatic
Pulmonary function testing
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Oncology
DLCO
030220 oncology & carcinogenesis
Diffusing capacity
Anesthesia
Medicine
Dosing
medicine.symptom
business
Cohort study
Subjects
Details
- ISSN :
- 15560864
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Journal of Thoracic Oncology
- Accession number :
- edsair.doi...........539bb90f20c928e6b0f130c0eb9d235a