2. Academic Validation
  3. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study

Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study

  • J Thorac Oncol. 2021 Sep;16(9):1547-1558. doi: 10.1016/j.jtho.2021.02.009.
Fiona Blackhall 1,  Kevin Jao 2,  Laurent Greillier 3,  Byoung Chul Cho 4,  Konstantin Penkov 5,  Noemi Reguart 6,  Margarita Majem 7,  Kristiaan Nackaerts 8,  Konstantinos Syrigos 9,  Karin Hansen 10,  Wolfgang Schuette 11,  Jeremy Cetnar 12,  Federico Cappuzzo 13,  Isamu Okamoto 14,  Mustafa Erman 15,  Seppo W Langer 16,  Terufumi Kato 17,  Harry Groen 18,  Zhaowen Sun 19,  Yan Luo 19,  Poonam Tanwani 19,  Laura Caffrey 19,  Philip Komarnitsky 19,  Niels Reinmuth 20
Affiliations

Affiliations

  • 1 Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom; Department of Medical Oncology, The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom. Electronic address: Fiona.Blackhall@nhs.net.
  • 2 Department of Hematology and Oncology, Hopital du Sacre Coeur Montreal, Montreal, Canada.
  • 3 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, Marseille, France.
  • 4 Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
  • 5 Private Medical Institution Euromedservice, St. Petersburg, Russia.
  • 6 Department of Medical Oncology, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic de Barcelona, Barcelona, Spain.
  • 7 Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • 8 Department of Pulmonology and Respiratory Oncology, University Hospital Leuven, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.
  • 9 Department of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • 10 Department of Oncology, Odense Universitets Hospital, Odense, Denmark.
  • 11 2nd Medical Department, Krankenhaus Martha-Maria Halle-Doelau, Halle, Germany.
  • 12 Department of Medicine, Oregon Health & Science University, Portland, Oregon.
  • 13 Department of Medical Oncology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
  • 14 Department of Medical Oncology, Kyushu University Hospital, Fukuoka, Japan.
  • 15 Department of Medical Oncology, Cancer Institute, Hacettepe University, Ankara, Turkey.
  • 16 Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • 17 Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.
  • 18 Department of Pulmonary Disease, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
  • 19 AbbVie, Inc., North Chicago, Illinois.
  • 20 Thoracic Oncology Department, Asklepios Fachkliniken München-Gauting, Gauting, Germany.
PMID: 33607312 DOI: 10.1016/j.jtho.2021.02.009
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/m2) 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.

Keywords

Delta-like protein 3; Rovalpituzumab tesirine; Small cell lung cancer; Topotecan.

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