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

Scott N. Gettinger, MD; Rudolf M. Huber, MD, PhD; Dong-Wan Kim, MD, PhD; Lyudmila Bazhenova, MD; Karin Holmskov Hansen, MD; Marcello Tiseo, MD; Corey J. Langer, MD, FACP; Luis G. Paz-Ares Rodríguez, MD, PhD; Howard L. West, MD; Karen L. Reckamp, MD, MS; Glen J. Weiss, MD; Egbert F. Smit, MD, PhD; Maximilian J. Hochmair, MD; Sang-We Kim, MD, PhD; Myung-Ju Ahn, MD, PhD; Edward S. Kim, MD, FACP; Harry J.M. Groen, MD, PhD; Joanna Pye, MS; Yuyin Liu, PhD; Pingkuan Zhang, MD; Florin Vranceanu, MD, PhD; D. Ross Camidge, MD, PhD

JTO Clinical and Research Reports (Sep 2022)

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

Scott N. Gettinger, MD,
Rudolf M. Huber, MD, PhD,
Dong-Wan Kim, MD, PhD,
Lyudmila Bazhenova, MD,
Karin Holmskov Hansen, MD,
Marcello Tiseo, MD,
Corey J. Langer, MD, FACP,
Luis G. Paz-Ares Rodríguez, MD, PhD,
Howard L. West, MD,
Karen L. Reckamp, MD, MS,
Glen J. Weiss, MD,
Egbert F. Smit, MD, PhD,
Maximilian J. Hochmair, MD,
Sang-We Kim, MD, PhD,
Myung-Ju Ahn, MD, PhD,
Edward S. Kim, MD, FACP,
Harry J.M. Groen, MD, PhD,
Joanna Pye, MS,
Yuyin Liu, PhD,
Pingkuan Zhang, MD,
Florin Vranceanu, MD, PhD,
D. Ross Camidge, MD, PhD

Affiliations

Scott N. Gettinger, MD: Yale Cancer Center, Yale-New Haven Hospital, New Haven, Connecticut; Corresponding author. Address for correspondence: Scott N. Gettinger, MD, Yale Cancer Center, Yale-New Haven Hospital, 333 Cedar Street, FMP 127, New Haven, CT 06520-8028.
Rudolf M. Huber, MD, PhD: Thoracic Oncology Centre Munich, University Hospital of Munich, member of the German Center for Lung Research (DZL, CPC-M), Munich, Germany
Dong-Wan Kim, MD, PhD: Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea
Lyudmila Bazhenova, MD: University of California San Diego Moores Cancer Center, La Jolla, California
Karin Holmskov Hansen, MD: Department of Clinical Oncology, Odense University Hospital, Odense, Denmark
Marcello Tiseo, MD: Department of Medicine and Surgery, University of Parma, Parma, Italy
Corey J. Langer, MD, FACP: University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania
Luis G. Paz-Ares Rodríguez, MD, PhD: Medical Oncology Department, Hospital Universitario, Madrid, Spain
Howard L. West, MD: City of Hope Comprehensive Cancer Center, Duarte, California
Karen L. Reckamp, MD, MS: City of Hope Comprehensive Cancer Center, Duarte, California; Current Affiliation: Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, California
Glen J. Weiss, MD: MiRanostics Consulting, Oro Valley, Arizona
Egbert F. Smit, MD, PhD: Thoracic Oncology Service, Netherlands Cancer Institute, Amsterdam, The Netherlands
Maximilian J. Hochmair, MD: Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Department of Respiratory and Critical Care Medicine, Klinik Floridsdorf, Vienna, Austria
Sang-We Kim, MD, PhD: Department of Oncology, Asan Medical Center, Seoul, South Korea
Myung-Ju Ahn, MD, PhD: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Edward S. Kim, MD, FACP: City of Hope Comprehensive Cancer Center, Duarte, California
Harry J.M. Groen, MD, PhD: Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
Joanna Pye, MS: Oncology Statistics, Takeda Development Center Americas, Inc., Lexington, Massachusetts
Yuyin Liu, PhD: Oncology Statistics, Takeda Development Center Americas, Inc., Lexington, Massachusetts
Pingkuan Zhang, MD: Clinical Science, Takeda Development Center Americas, Inc., Lexington, Massachusetts; Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, Colorado
Florin Vranceanu, MD, PhD: Oncology Statistics, Takeda Development Center Americas, Inc., Lexington, Massachusetts; Clinical Science, Takeda Development Center Americas, Inc., Lexington, Massachusetts
D. Ross Camidge, MD, PhD: Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, Colorado

Journal volume & issue: Vol. 3, no. 9
p. 100385

Abstract

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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.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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