Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC : Results From the Phase 3 TAHOE Study
Blackhall, Fiona (Department of Medical Oncology. The Christie National Health Service (NHS) Foundation Trust)
Jao, Kevin (Department of Hematology and Oncology. Hopital du Sacre Coeur Montreal)
Greillier, Laurent (Multidisciplinary Oncology and Therapeutic Innovations Department. Centre de Recherche en Cancérologie de Marseille (CRCM). Centre National de la Recherche Scientifique (CNRS). Institut National de la Santé et de la Recherche Médicale (INSERM). Assistance Publique-Hopitaux de Marseille (APHM). Aix-Marseille University)
Cho, Byoung Chul (Division of Medical Oncology. Department of Internal Medicine. Yonsei Cancer Center. Yonsei University College of Medicine)
Penkov, Konstantin (Private Medical Institution Euromedservice)
Reguart, Noemi (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Majem, Margarita (Institut d'Investigació Biomèdica Sant Pau)
Nackaerts, Kristiaan (Department of Pulmonology and Respiratory Oncology. University Hospital Leuven. Katholieke Universiteit (KU) Leuven)
Syrigos, Konstantinos (Department of Medicine. National and Kapodistrian University of Athens)
Hansen, Karin (Odense University Hospital (Dinamarca))
Schuette, Wolfgang (2nd Medical Department. Krankenhaus Martha-Maria Halle-Doelau. Halle)
Cetnar, Jeremy (Department of Medicine. Oregon Health & Science University)
Cappuzzo, Federico (Department of Medical Oncology. Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS))
Okamoto, Isamu (Department of Medical Oncology. Kyushu University Hospital)
Erman, Mustafa (Department of Medical Oncology. Cancer Institute. Hacettepe University)
Langer, Seppo W. (Rigshospitalet. University of Copenhagen)
Kato, Terufumi (Kanagawa Cancer Center)
Groen, Harry (Department of Pulmonary Disease. University Medical Center Groningen. University of Groningen)
Sun, Zhaowen (AbbVie. Inc.)
Luo, Yan (AbbVie. Inc.)
Tanwani, Poonam (AbbVie. Inc.)
Caffrey, Laura (AbbVie. Inc.)
Komarnitsky, Philip (AbbVie. Inc.)
Reinmuth, Niels (Thoracic Oncology Department. Asklepios Fachkliniken München-Gauting)

Date:	2021
Abstract:	Introduction: DLL3, an atypical Notch ligand, is expressed in SCLC tumors but is not detectable in normal adult tissues. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate containing a DLL3-targeting antibody tethered to a cytotoxic agent pyrrolobenzodiazepine by means of a protease-cleavable linker. The efficacy and safety of Rova-T compared with topotecan as second-line therapy in patients with SCLC expressing high levels of DLL3 (DLL3-high) was evaluated. Methods: The TAHOE study was an open-label, two-to-one randomized, phase 3 study comparing Rova-T with topotecan as second-line therapy in DLL3-high advanced or metastatic SCLC. Rova-T (0. 3 mg/kg) was administered intravenously on day 1 of a 42-day cycle for two cycles, with two additional cycles available to patients who met protocol-defined criteria for continued dosing. Topotecan (1. 5 mg/m) was administered intravenously on days 1 to 5 of a 21-day cycle. The primary end point was overall survival (OS). Results: Patients randomized to Rova-T (n = 296) and topotecan (n = 148) were included in the efficacy analyses. The median age was 64 years, and 77% had the extensive disease at initial diagnosis. The median OS (95% confidence interval) was 6. 3 months (5. 6-7. 3) in the Rova-T arm and 8. 6 months (7. 7-10. 1) in the topotecan arm (hazard ratio, 1. 46 [95% confidence interval: 1. 17-1. 82]). An independent data monitoring committee recommended that enrollment be discontinued because of the shorter OS observed with Rova-T compared with topotecan. Safety profiles for both drugs were consistent with previous reports. Conclusions: Compared with topotecan, which is the current standard second-line chemotherapy, Rova-T exhibited an inferior OS and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC. A considerable unmet therapeutic need remains in this population.
Note:	Altres ajuts: AbbVie, Inc.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Small cell lung cancer ; Rovalpituzumab tesirine ; Delta-like protein 3 ; Topotecan
Published in:	Journal of Thoracic Oncology, Vol. 16 Núm. 9 (september 2021) , p. 1547-1558, ISSN 1556-1380

DOI: 10.1016/j.jtho.2021.02.009
PMID: 33607312

12 p, 339.3 KB

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