TY - JOUR
T1 - Short communication
T2 - The activity of brigatinib in patients with disease progression after next generation anaplastic lymphoma tyrosine kinase inhibitors and an exploratory analysis of circulating tumor DNA
AU - Stinchcombe, Thomas E.
AU - Wang, Xiaofei
AU - Doebele, Robert C.
AU - Drusbosky, Leylah M.
AU - Gerber, David E.
AU - Horn, Leora
AU - Bertino, Erin M.
AU - Liu, Geoff
AU - Villaruz, Liza C.
AU - Ross Camidge, D.
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2022/3
Y1 - 2022/3
N2 - Background: Brigatinib, a second generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), is central nervous system (CNS) penetrant and active against anaplastic lymphoma kinase (ALK) resistance mutations. We prospectively studied the activity of brigatinib in patients with disease progression after second generation ALK TKIs. Methods: Patients with stage IIIB/IV ALK + non-small cell lung cancer (NSCLC), and progressive disease after second ALK TKIs were eligible. Cohort A enrolled patients with disease progression on any second ALK TKI, cohort B enrolled patients with disease progression after first-line therapy with alectinib, and cohort C enrolled patients who experienced disease progression on standard dose brigatinib. Brigatinib treatment was 90 mg daily for seven days and then escalated to 180 mg daily in cohorts A and B, and 240 mg daily in cohort C. The primary endpoint was objective response rate (ORR), and a 2-stage design was used. The intended enrollment was 20 patients in stage 1, and 20 patients in stage 2. Results: The study was closed due to slow accrual. Between March 2017 and June 2020, 32 patients received study therapy; three patients in cohort A moved to cohort C after initial progression for a total of 35 study subjects. Of the 32 patients, 16 (50%) were male, the median age was 55 years (range 32–76), and patients received a median number of 2 prior ALK TKI's (range 1–3). Cohort A enrolled 27 patients, cohort B enrolled four patients, and cohort C enrolled four patients. The ORR in cohorts A, B, and C was 33% (95% confidence interval (CI: 16% to 54%), 25% (95% CI: 0.63% to 81%), and 0%, respectively. Conclusion: Brigatinib has activity in ALK positive NSCLC patients with disease progression after second generation ALK TKIs.
AB - Background: Brigatinib, a second generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), is central nervous system (CNS) penetrant and active against anaplastic lymphoma kinase (ALK) resistance mutations. We prospectively studied the activity of brigatinib in patients with disease progression after second generation ALK TKIs. Methods: Patients with stage IIIB/IV ALK + non-small cell lung cancer (NSCLC), and progressive disease after second ALK TKIs were eligible. Cohort A enrolled patients with disease progression on any second ALK TKI, cohort B enrolled patients with disease progression after first-line therapy with alectinib, and cohort C enrolled patients who experienced disease progression on standard dose brigatinib. Brigatinib treatment was 90 mg daily for seven days and then escalated to 180 mg daily in cohorts A and B, and 240 mg daily in cohort C. The primary endpoint was objective response rate (ORR), and a 2-stage design was used. The intended enrollment was 20 patients in stage 1, and 20 patients in stage 2. Results: The study was closed due to slow accrual. Between March 2017 and June 2020, 32 patients received study therapy; three patients in cohort A moved to cohort C after initial progression for a total of 35 study subjects. Of the 32 patients, 16 (50%) were male, the median age was 55 years (range 32–76), and patients received a median number of 2 prior ALK TKI's (range 1–3). Cohort A enrolled 27 patients, cohort B enrolled four patients, and cohort C enrolled four patients. The ORR in cohorts A, B, and C was 33% (95% confidence interval (CI: 16% to 54%), 25% (95% CI: 0.63% to 81%), and 0%, respectively. Conclusion: Brigatinib has activity in ALK positive NSCLC patients with disease progression after second generation ALK TKIs.
KW - Biomarker
KW - Liquid biopsy
KW - Targeted therapy
KW - ctDNA
UR - http://www.scopus.com/inward/record.url?scp=85123299362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123299362&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2021.12.019
DO - 10.1016/j.lungcan.2021.12.019
M3 - Article
C2 - 35085983
AN - SCOPUS:85123299362
SN - 0169-5002
VL - 165
SP - 43
EP - 48
JO - Lung Cancer
JF - Lung Cancer
ER -