@article{3030827,
    title = "Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan
as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE
Study",
    author = "Blackhall, Fiona and Jao, Kevin and Greillier, Laurent and Cho, Byoung and Chul and Penkov, Konstantin and Reguart, Noemi and Majem, Margarita and and Nackaerts, Kristiaan and Syrigos, Konstantinos and Hansen, Karin and and Schuette, Wolfgang and Cetnar, Jeremy and Cappuzzo, Federico and and Okamoto, Isamu and Erman, Mustafa and Langer, Seppo W. and Kato, and Terufumi and Groen, Harry and Sun, Zhaowen and Luo, Yan and Tanwani, and Poonam and Caffrey, Laura and Komarnitsky, Philip and Reinmuth, Niels",
    journal = "Journal of Thoracic Oncology",
    year = "2021",
    volume = "16",
    number = "9",
    pages = "1547-1558",
    publisher = "EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC",
    issn = "1556-0864, 1556-1380",
    doi = "10.1016/j.jtho.2021.02.009",
    keywords = "Small cell lung cancer; Rovalpituzumab tesirine; Delta-like protein 3;
Topotecan",
    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(2))
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. (C) 2021 International Association for the
Study of Lung Cancer. Published by Elsevier Inc."
}