Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With <i>NTRK</i> Fusion-Positive Solid Tumors
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- George D. Demetri
- 1Dana-Farber Cancer Institute and Ludwig Center at Harvard Medical School, Boston, Massachusetts.
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- Filippo De Braud
- 2Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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- Alexander Drilon
- 4Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, New York.
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- Salvatore Siena
- 3Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
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- Manish R. Patel
- 6Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
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- Byoung Chul Cho
- 7Yonsei Cancer Hospital, Seoul, Republic of Korea.
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- Stephen V. Liu
- 8Georgetown University, Washington, D.C.
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- Myung-Ju Ahn
- 9Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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- Chao-Hua Chiu
- 10Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
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- Jessica J. Lin
- 11Massachusetts General Hospital, Boston, Massachusetts.
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- Koichi Goto
- 12National Cancer Center Hospital East, Kashiwa, Japan.
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- Jeeyun Lee
- 9Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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- Lyudmila Bazhenova
- 13University of California San Diego, San Diego, California.
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- Thomas John
- 14Peter MacCallum Cancer Center, and Olivia Newton-John Cancer Centre, Austin Health, Melbourne, Australia.
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- Marwan Fakih
- 15City of Hope Comprehensive Cancer Center, Duarte, California.
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- Sant P. Chawla
- 16Sarcoma Oncology Center, Santa Monica, California.
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- Rafal Dziadziuszko
- 17Department of Oncology and Radiotherapy and Early Clinical Trials Unit, Medical University of Gdansk, Gdansk, Poland.
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- Takashi Seto
- 18National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
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- Sebastian Heinzmann
- 19F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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- Bethany Pitcher
- 20F. Hoffmann-La Roche Ltd, Mississauga, Canada.
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- David Chen
- 21Genentech Inc., South San Francisco, California.
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- Timothy R. Wilson
- 21Genentech Inc., South San Francisco, California.
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- Christian Rolfo
- 22Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
説明
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>Entrectinib potently inhibits tropomyosin receptor kinases (TRKAs)/B/C and ROS1, and previously induced deep [objective response rate (ORR) 57.4%] and durable [median duration of response (DoR) 10.4 months] responses in adults with NTRK fusion-positive solid tumors from three phase I/II trials. This article expands prior reports with additional patients and longer follow-up.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and Methods:</jats:title> <jats:p>Patients with locally advanced/metastatic NTRK fusion-positive solid tumors and ≥12 months' follow-up were included. Primary endpoints were ORR and DoR by blinded independent central review (BICR); secondary endpoints included progression-free survival (PFS), intracranial efficacy, and safety. The safety-evaluable populations included all patients who had received ≥1 entrectinib dose.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>At clinical cut-off (August 31, 2020), the efficacy-evaluable population comprised 121 adults with 14 tumor types and ≥30 histologies. Median follow-up was 25.8 months; 61.2% of patients had a complete (n = 19) or partial response (n = 55). Median DoR was 20.0 months [95% confidence interval (CI), 13.0–38.2]; median PFS was 13.8 months (95% CI, 10.1–19.9). In 11 patients with BICR-assessed measurable central nervous system (CNS) disease, intracranial ORR was 63.6% (95% CI, 30.8–89.1) and median intracranial DoR was 22.1 (95% CI, 7.4–not estimable) months. The safety profile of entrectinib in adults and pediatric patients was aligned with previous reports. Most treatment-related adverse events (TRAEs) were grade 1/2 and manageable/reversible with dose modifications. TRAE-related discontinuations occurred in 8.3% of patients.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>With additional clinical experience, entrectinib continues to demonstrate durable systemic and intracranial responses and can address the unmet need of a CNS-active treatment in patients with NTRK fusion-positive solid tumors.</jats:p> </jats:sec>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 28 (7), 1302-1312, 2022-02-10
American Association for Cancer Research (AACR)