Abstract
Original language | English |
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Pages (from-to) | 404-415 |
Number of pages | 12 |
Journal | Journal of Thoracic Oncology |
Volume | 15 |
Issue number | 3 |
Early online date | Nov 2019 |
DOIs | |
Publication status | Published - 1 Mar 2020 |
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Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial. / Huber, Rudolf M.; Hansen, Karin H.; Paz-Ares Rodríguez, Luis et al.
In: Journal of Thoracic Oncology, Vol. 15, No. 3, 01.03.2020, p. 404-415.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial
AU - Huber, Rudolf M.
AU - Hansen, Karin H.
AU - Paz-Ares Rodríguez, Luis
AU - West, Howard L.
AU - Reckamp, Karen L.
AU - Leighl, Natasha B.
AU - Tiseo, Marcello
AU - Smit, Egbert F.
AU - Kim, Dong-Wan
AU - Gettinger, Scott N.
AU - Hochmair, Maximilian J.
AU - Kim, Sang-We
AU - Langer, Corey J.
AU - Ahn, Myung-Ju
AU - Kim, Edward S.
AU - Kerstein, David
AU - Groen, Harry J. M.
AU - Camidge, D. Ross
N1 - Funding Information: Disclosure: Dr. Huber received personal fees from Takeda/ARIAD during the conduct of the study, and has received personal fees from AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Clovis, Lilly, MSD, Novartis, Pfizer, Roche, and Takeda/ARIAD. Dr. Hansen has received personal fees as an advisory board member from AstraZeneca, BMS, MSD, Pierre Fabre, Roche, and Takeda, as a speaker from Roche and Takeda, and as a consultant for Roche. Dr. Paz-Ares Rodr?guez has received personal fees from Adacap, Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer Ingelheim, Celgene, Incyte, Ipsen, Lilly, Merck, MSD, Novartis, Pfizer, Pharmamar, Roche, Sanofi, Servier, and Sysmex as a scientific advisor/speaker; has received grants from AstraZeneca, BMS, MSD, and Pfizer as a scientific advisor/speaker; and is an advisory board member for Gen?mica and a cofounder and board member for Altum Sequencing. Dr. West has received personal fees as an advisory board member, consultant, and speaker for Genentech/Roche and Takeda/ARIAD, and as a consultant and speaker for Novartis and Pfizer. Dr. Reckamp has received research grants/personal fees from Boehringer Ingelheim, Genentech, Guardant, Loxo, Seattle Genetics, and Takeda (all to institution) as a consultant; has received research grants from Acea, Adaptimmune, BMS, GlaxoSmithKline, Janssen, Pfizer, Xcovery, and Zeno (all to institution); has received a grant from Exelixis as a consultant; and has received personal fees from AstraZeneca and Tesaro as a consultant. Dr. Tiseo has received grants from AstraZeneca, BMS, Boehringer Ingelheim, MSD, and Takeda as an advisory board member, and has received research grants from AstraZeneca and Boehringer Ingelheim. Dr. Smit has received fees from Takeda (to his institution) as an advisory board member. Dr. D.-W. Kim has received a grant and nonfinancial support from Takeda for clinical trial funding and editorial support. Dr. Gettinger has received personal fees from BMS and Nektar Research Funding as a consultant and advisory board member, and has received research funding from BMS, Genentech/Roche, Iovance, and Takeda/ARIAD. Dr. Hochmair has received personal fees/honoraria from AstraZeneca, Boehringer Ingelheim, MSD, Pfizer, Roche, and Takeda as a speaker. Dr. Langer has received grant/research support from Advantagene, ARIAD (Takeda), Genentech, GSK, Guardant Health, Inovio, Lilly, Merck, Nektar, Pfizer, and StemCentrx (Takai); has served as a scientific advisor for AbbVie, ARIAD (Takeda), AstraZeneca, Bayer/Onyx, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Gilead, Helsinn, Hospira, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche/Genentech, Takai, and Tmunity; has served on the Data and Safety Monitoring Committee for Amgen, Lilly, SWOG, and Synta; and has received fees from CCO, Imedex, MLG, NOCR, PER, PIK, RTP, TRM, and Web-MD as a continuing medical education chair/lecturer. Dr. Kerstein reports employment at Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Dr. Groen has received research funding from Lilly, Novartis, Roche-Genentech, and Takeda (all to institution). Dr. Camidge has received honoraria from Genentech/Roche, Novartis, Pfizer, and Takeda, and received a grant from Takeda for institutional trial support. Dr. Leighl, Dr. S.-W. Kim, Dr. Ahn, and Dr. E.S. Kim declare no conflict of interest.This study was sponsored by ARIAD Pharmaceuticals, Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. The trial was designed by the sponsor, ARIAD Pharmaceuticals, Inc. in collaboration with the senior author. Data were collected and trial procedures were overseen by the trial investigators. The sponsor analyzed the data and funded medical writing assistance and publication charges. The authors thank the patients, their families and caregivers, and the investigators and their team members for participation in the ALTA trial. The authors also thank the members of the study team (ARIAD Pharmaceuticals) and Janice Y. Ahn, PhD (formerly of Millennium Pharmaceuticals, Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited) for editorial assistance. William Reichmann, PhD (formerly of Millennium Pharmaceuticals, Inc.) is acknowledged for his contributions to the analysis. Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, and Lela Creutz, PhD (Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ) and funded by Millennium Pharmaceuticals, Inc. DRC was partially supported by the University of Colorado Lung Cancer SPORE (P50CA058187). Funding Information: This study was sponsored by ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. The trial was designed by the sponsor, ARIAD Pharmaceuticals, Inc., in collaboration with the senior author. Data were collected and trial procedures were overseen by the trial investigators. The sponsor analyzed the data and funded medical writing assistance and publication charges. The authors thank the patients, their families and caregivers, and the investigators and their team members for participation in the ALTA trial. The authors also thank the members of the study team (ARIAD Pharmaceuticals) and Janice Y. Ahn, PhD (formerly of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited) for editorial assistance. William Reichmann, PhD (formerly of Millennium Pharmaceuticals, Inc.) is acknowledged for his contributions to the analysis. Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, and Lela Creutz, PhD (Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ) and funded by Millennium Pharmaceuticals , Inc. DRC was partially supported by the University of Colorado Lung Cancer SPORE ( P50CA058187 ). Publisher Copyright: © 2019 International Association for the Study of Lung Cancer Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Introduction: We report updated data from a phase 2 randomized study evaluating brigatinib in crizotinib-refractory anaplastic lymphoma kinase–positive NSCLC. Methods: Patients were randomized 1:1 to take either oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (arm B), stratified by central nervous system (CNS) metastases and best response to crizotinib. The primary end point was investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included independent review committee (IRC)-assessed progression-free survival (PFS), intracranial PFS (iPFS), and overall survival (OS). Exploratory analyses included CNS versus ex-CNS target lesion response and correlation of depth of response with PFS and OS. Results: Among 222 randomized patients (112 and 110 in arms A and B, respectively), 59 (27%) remained on brigatinib at analysis (median follow-up: 19.6 versus 24.3 months). At baseline, 71% and 67% had brain lesions among A and B arms, respectively. Investigator-assessed confirmed objective response rate was 46% versus 56%. Median IRC-assessed PFS was 9.2 months (95% confidence interval: 7.4–12.8) versus 16.7 months (11.6–21.4). Median OS was 29.5 months (18.2–not reached) versus 34.1 months (27.7–not reached). IRC-confirmed intracranial objective response rate in patients with measurable baseline brain lesions was 50% (13 of 26) versus 67% (12 of 18); median duration of intracranial response was 9.4 versus 16.6 months. IRC-assessed iPFS was 12.8 versus 18.4 months. Across arms, median IRC-assessed PFS was 1.9, 5.5, 11.1, 16.7, and 15.6 months for patients with no, 1%–25%, 26%–50%, 51%–75%, and 76%–100% target lesion shrinkage, respectively. No new safety findings were observed with longer follow-up. Conclusions: Brigatinib (180 mg once daily with lead-in) continues to demonstrate robust PFS, long iPFS and duration of intracranial response, and high intracranial objective response rate in crizotinib-refractory patients. Depth of response may be an important end point to capture in future targeted therapy trials.
AB - Introduction: We report updated data from a phase 2 randomized study evaluating brigatinib in crizotinib-refractory anaplastic lymphoma kinase–positive NSCLC. Methods: Patients were randomized 1:1 to take either oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (arm B), stratified by central nervous system (CNS) metastases and best response to crizotinib. The primary end point was investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included independent review committee (IRC)-assessed progression-free survival (PFS), intracranial PFS (iPFS), and overall survival (OS). Exploratory analyses included CNS versus ex-CNS target lesion response and correlation of depth of response with PFS and OS. Results: Among 222 randomized patients (112 and 110 in arms A and B, respectively), 59 (27%) remained on brigatinib at analysis (median follow-up: 19.6 versus 24.3 months). At baseline, 71% and 67% had brain lesions among A and B arms, respectively. Investigator-assessed confirmed objective response rate was 46% versus 56%. Median IRC-assessed PFS was 9.2 months (95% confidence interval: 7.4–12.8) versus 16.7 months (11.6–21.4). Median OS was 29.5 months (18.2–not reached) versus 34.1 months (27.7–not reached). IRC-confirmed intracranial objective response rate in patients with measurable baseline brain lesions was 50% (13 of 26) versus 67% (12 of 18); median duration of intracranial response was 9.4 versus 16.6 months. IRC-assessed iPFS was 12.8 versus 18.4 months. Across arms, median IRC-assessed PFS was 1.9, 5.5, 11.1, 16.7, and 15.6 months for patients with no, 1%–25%, 26%–50%, 51%–75%, and 76%–100% target lesion shrinkage, respectively. No new safety findings were observed with longer follow-up. Conclusions: Brigatinib (180 mg once daily with lead-in) continues to demonstrate robust PFS, long iPFS and duration of intracranial response, and high intracranial objective response rate in crizotinib-refractory patients. Depth of response may be an important end point to capture in future targeted therapy trials.
KW - ALK tyrosine kinase receptor
KW - Anaplastic lymphoma kinase
KW - Brigatinib
KW - Non–small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=85078003185&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2019.11.004
DO - 10.1016/j.jtho.2019.11.004
M3 - Article
C2 - 31756496
VL - 15
SP - 404
EP - 415
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 3
ER -