Abstract
| Original language | English |
|---|---|
| Article number | 100385 |
| Journal | JTO Clinical and Research Reports |
| Volume | 3 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 1 Sept 2022 |
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Long-Term Efficacy and Safety of Brigatinib in Crizotinib-Refractory ALK+ NSCLC : Final Results of the Phase 1/2 and Randomized Phase 2 (ALTA) Trials. / Gettinger, Scott N.; Huber, Rudolf M.; Kim, Dong-Wan et al.
In: JTO Clinical and Research Reports, Vol. 3, No. 9, 100385, 01.09.2022.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Long-Term Efficacy and Safety of Brigatinib in Crizotinib-Refractory ALK+ NSCLC
T2 - Final Results of the Phase 1/2 and Randomized Phase 2 (ALTA) Trials
AU - Gettinger, Scott N.
AU - Huber, Rudolf M.
AU - Kim, Dong-Wan
AU - Bazhenova, Lyudmila
AU - Hansen, Karin Holmskov
AU - Tiseo, Marcello
AU - Langer, Corey J.
AU - Paz-Ares Rodríguez, Luis G.
AU - West, Howard L.
AU - Reckamp, Karen L.
AU - Weiss, Glen J.
AU - Smit, Egbert F.
AU - Hochmair, Maximilian J.
AU - Kim, Sang-We
AU - Ahn, Myung-Ju
AU - Kim, Edward S.
AU - Groen, Harry J. M.
AU - Pye, Joanna
AU - Liu, Yuyin
AU - Zhang, Pingkuan
AU - Vranceanu, Florin
AU - Camidge, D. Ross
N1 - Funding Information: This study was sponsored by ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. The sponsor designed and conducted the study and collected the data together with the authors. The sponsor managed and analyzed the data. Data were interpreted by the authors and the sponsor. The sponsor together with the authors prepared, reviewed, and approved the manuscript and made the decision to submit the manuscript for publication. The authors thank the patients, their families, and their caregivers; the investigators and their team members at each study site; and colleagues from ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, and Lela Creutz, PhD, of Peloton Advantage, LLC, an OPEN Health Company, Parsippany, New Jersey, and funded by Millennium Pharmaceuticals, Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. The authors thank Teodor G. Paunescu, PhD (Takeda Pharmaceuticals USA, Inc.), for editorial assistance. Funding Information: This study was sponsored by ARIAD Pharmaceuticals, Inc. Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. The sponsor designed and conducted the study and collected the data together with the authors. The sponsor managed and analyzed the data. Data were interpreted by the authors and the sponsor. The sponsor together with the authors prepared, reviewed, and approved the manuscript and made the decision to submit the manuscript for publication. The authors thank the patients, their families, and their caregivers; the investigators and their team members at each study site; and colleagues from ARIAD Pharmaceuticals, Inc. Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, and Lela Creutz, PhD, of Peloton Advantage, LLC, an OPEN Health Company, Parsippany, New Jersey, and funded by Millennium Pharmaceuticals, Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. The authors thank Teodor G. Paunescu, PhD (Takeda Pharmaceuticals USA, Inc.), for editorial assistance. Disclosure: Dr. Gettinger reports receiving research funding from ARIAD/Takeda, Bristol Myers Squibb, Roche/Genentech, NextCure, and Iovance. Dr. Huber reports receiving honoraria from ARIAD, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, and Roche; having consulting or advisory role for BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Clovis Oncology, Eli Lilly, Novartis, Roche, and Sanofi; and receiving research funding from AstraZeneca. Dr. D.-W. Kim reports receiving research funding to institution from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, Daiichi Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan; and travel/accommodation support from Amgen and Daiichi Sankyo. Bazhenova reports having stock and other ownership interests from Epic Sciences; having consulting or advisory role from ARIAD, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Novartis, Blueprint Medicines, BeyondSpring, G1 Therapeutics, Bayer, Boehringer Ingelheim, Regeneron, Merck, Johnson & Johnson, Daiichi Sankyo, and Neuvogen; and receiving research funding from BeyondSpring. Dr. Tiseo reports having speakers’ bureau or advisory role for AstraZeneca, Pfizer, Eli Lilly, Bristol Myers Squibb, Novartis, Roche, Merck Sharp & Dohme, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, and Merck; and receiving research grants from AstraZeneca and Boehringer Ingelheim. Dr. Langer reports receiving honoraria from Eli Lilly, Roche/Genentech, AstraZeneca, Takeda, and Merck; having consulting or advisory role from Abbott, AstraZeneca, Bayer/Onyx, Bristol Myers Squibb, Cancer Support Community, Celgene, Clarient, Eli Lilly, Merck, Gilead, Roche/Genentech, Takeda, Pfizer, and Novocure; receiving research funding from Advantagene, Amgen, ARIAD, Celgene, Clovis Oncology, GlaxoSmithKline, Inovio, Merck, Roche/Genentech, Lilly, and Trizell; and having other relationship from Amgen, Lilly, Peregrine Pharmaceuticals, and Synta. Dr. Paz-Ares Rodríguez reports having leadership role from Genomica and Altum Sequencing; having speakers’ bureau from Merck Sharp & Dohme Oncology, Bristol Myers Squibb, Roche/Genentech, Pfizer, Lilly, AstraZeneca, and Merck Serono; receiving travel, accommodation, and expenses from Roche, AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb, Pfizer, and Takeda; receiving other support from Novartis, Ipsen, Pfizer, Servier Sanofi, Roche, Amgen, and Merck; receiving honoraria from Roche/Genentech, Lilly, Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Merck Serono, PharmaMar, Novartis, Celgene, Amgen, Sanofi, Ipsen, Servier, Bayer, Blueprint Medicines, Mirati Therapeutics, and Takeda; and receiving research funding from Bristol Myers Squibb, AstraZeneca, PharmaMar, Kura Oncology, and Merck Sharp & Dohme. Dr. West reports having consulting or advisory role from Amgen, AstraZeneca, Merck, Roche/Genentech, Mirati, Pfizer, Regeneron, and Takeda; having speakers’ bureau from AstraZeneca and Merck; and receiving honoraria from Amgen, AstraZeneca, Merck, Roche/Genentech, Mirati, Pfizer, Regeneron, and Takeda. Dr. Reckamp reports having consulting/advisory role from Amgen, Takeda, AstraZeneca, Boehringer Ingelheim, Calithera Biosciences, Seattle Genetics, Tesaro, Genentech, Blueprint Medicines, Daiichi Sankyo/Lilly, EMD Serono, Janssen Oncology, Lilly, and Merck KGaA; and receiving research funding, all to institution, from AbbVie, ACEA Biosciences, Adaptimmune, ARIAD, Boehringer Ingelheim, Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, Guardant Health, Janssen Oncology, Loxo, Pfizer, Seattle Genetics, Xcovery, Zeno Pharmaceuticals, Calithera Biosciences, and Elevation Oncology. Dr. Weiss reports having employment from SOTIO, LLC; having former employment from Unum Therapeutics; having consulting or advisory role from Paradigm, Viomics, Circulogene, GLG Council, Angiex, Guidepoint Global, Imaging Endpoints II, MiRanostics Consulting, International Genomics Consortium, IBEX Medical Analytics, Genomic Health, Gossamer Bio, SPARC, Oncacare, and Rafael Therapeutics; having stock and other ownership interests from Circulogene, Unum Therapeutics, Exact Sciences, Moderna MiRanostics Consulting, Aurinia Pharmaceuticals, and Cogent Biosciences; and has issued patents PCT/US2008/072787, PCT/US2010/043777, PCT/US2011/020612, and PCT/US20211037616, all outside this submitted work. Dr. Smit reports having consulting or advisory role from Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol Myers Squibb, Merck KGaA, Merck Sharp & Dohme Oncology, Takeda, Bayer, Novartis, Daiichi Sankyo, and Seattle Genetics; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Roche/Genentech, and Bristol Myers Squibb. Dr. Hochmair reports receiving honoraria from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Roche, Takeda, and Merck Sharp & Dohme. Dr. S.-W. Kim reports receiving honoraria from AstraZeneca, Amgen, Boehringer Ingelheim, Janssen, Norvasc, Lilly, Takeda, and Yuhan; and receiving research funding from AstraZeneca and Boehringer Ingelheim. Dr. Ahn reports receiving honoraria from AstraZeneca, Merck Sharp & Dohme, Lilly, and Takeda; and having consulting or advisory role from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Lilly, Takeda, and Alpha Pharmaceutical. Dr. E. S. Kim reports having consulting or advisory role from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Takeda, and Roche/Genentech; receiving honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Takeda, and Roche/Genentech; receiving travel, accommodations, and expenses from AstraZeneca, Boehringer Ingelheim, Takeda, Genentech/Roche, Pfizer, and Merck; and receiving research funding from Boehringer Ingelheim, Merck, Ignyta, and Genentech/Roche. Dr. Groen reports having consulting or advisory role from Bristol Myers Squibb, Eli Lilly, Novartis, Roche/Genentech, and AstraZeneca; and receiving research funding from Roche and Boehringer Ingelheim. Ms. Pye, Drs. Liu, Zhang, and Vranceanu report having employment from Takeda. Dr. Camidge reports receiving honoraria from AstraZeneca, Takeda, Roche/Genentech, Daiichi Sankyo (ILD adjudication committee), Bio-Thera DSMB, Ribon Therapeutics, Bristol Myers Squibb, Inivata, AbbVie, Apollomics, Elevation Oncology, EMD Serono, Helsinn Therapeutics, Eli Lilly, Nuvalent, Seattle Genetics, and Turning Point Therapeutics. Dr. Hansen declares no conflict of interest. Publisher Copyright: © 2022 The Authors
PY - 2022/9/1
Y1 - 2022/9/1
N2 - Introduction: We report brigatinib long-term efficacy and safety from phase 1/2 and phase 2 (ALTA) trials in ALK–rearrangement positive (ALK+) NSCLC. Methods: The phase 1/2 study evaluated brigatinib 30 to 300 mg/d in patients with advanced malignancies. ALTA randomized patients with crizotinib-refractory ALK+ NSCLC to brigatinib 90 mg once daily (arm A) or 180 mg once daily (7-d lead-in at 90 mg; arm B). Results: In the phase 1/2 study, 79 of 137 brigatinib-treated patients had ALK+ NSCLC; 71 were crizotinib pretreated. ALTA randomized 222 patients (n = 112 in arm A; n = 110 in arm B). Median follow-up at phase 1/2 study end (≈5.6 y after last patient enrolled) was 27.7 months; at ALTA study end (≈4.4 y after last patient enrolled), 19.6 months (A) and 28.3 months (B). Among patients with ALK+ NSCLC in the phase 1/2 study, median investigator-assessed progression-free survival (PFS) was 14.5 months (95% confidence interval [CI]: 10.8–21.2); median overall survival was 47.6 months (28.6–not reached). In ALTA, median investigator-assessed PFS was 9.2 months (7.4–11.1) in arm A and 15.6 months (11.1–18.5) in arm B; median independent review committee (IRC)-assessed PFS was 9.9 (7.4–12.8) and 16.7 (11.6–21.4) months, respectively; median overall survival was 25.9 (18.2–45.8) and 40.6 (32.5–not reached) months, respectively. Median intracranial PFS for patients with any brain metastases was 12.8 (9.2–18.4) months in arm A and 18.4 (12.6–23.9) months in arm B. No new safety signals were identified versus previous analyses. Conclusions: Brigatinib exhibited sustained long-term activity and PFS with manageable safety in patients with crizotinib-refractory ALK+ NSCLC.
AB - Introduction: We report brigatinib long-term efficacy and safety from phase 1/2 and phase 2 (ALTA) trials in ALK–rearrangement positive (ALK+) NSCLC. Methods: The phase 1/2 study evaluated brigatinib 30 to 300 mg/d in patients with advanced malignancies. ALTA randomized patients with crizotinib-refractory ALK+ NSCLC to brigatinib 90 mg once daily (arm A) or 180 mg once daily (7-d lead-in at 90 mg; arm B). Results: In the phase 1/2 study, 79 of 137 brigatinib-treated patients had ALK+ NSCLC; 71 were crizotinib pretreated. ALTA randomized 222 patients (n = 112 in arm A; n = 110 in arm B). Median follow-up at phase 1/2 study end (≈5.6 y after last patient enrolled) was 27.7 months; at ALTA study end (≈4.4 y after last patient enrolled), 19.6 months (A) and 28.3 months (B). Among patients with ALK+ NSCLC in the phase 1/2 study, median investigator-assessed progression-free survival (PFS) was 14.5 months (95% confidence interval [CI]: 10.8–21.2); median overall survival was 47.6 months (28.6–not reached). In ALTA, median investigator-assessed PFS was 9.2 months (7.4–11.1) in arm A and 15.6 months (11.1–18.5) in arm B; median independent review committee (IRC)-assessed PFS was 9.9 (7.4–12.8) and 16.7 (11.6–21.4) months, respectively; median overall survival was 25.9 (18.2–45.8) and 40.6 (32.5–not reached) months, respectively. Median intracranial PFS for patients with any brain metastases was 12.8 (9.2–18.4) months in arm A and 18.4 (12.6–23.9) months in arm B. No new safety signals were identified versus previous analyses. Conclusions: Brigatinib exhibited sustained long-term activity and PFS with manageable safety in patients with crizotinib-refractory ALK+ NSCLC.
KW - ALK tyrosine kinase inhibitor
KW - Anaplastic lymphoma kinase
KW - Brigatinib
KW - Crizotinib
KW - Non–small-cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=85136559895&partnerID=8YFLogxK
U2 - 10.1016/j.jtocrr.2022.100385
DO - 10.1016/j.jtocrr.2022.100385
M3 - Article
C2 - 36065449
SN - 2666-3643
VL - 3
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
IS - 9
M1 - 100385
ER -