Efficacy and safety of rovalpituzumab tesirine compared with topotecan as second-line therapy in DLL3-high small cell lung cancer: results from the Phase 3 TAHOE study
AuthorsBlackhall, Fiona H
Cho, B. C.
Langer, S. W.
AffiliationUniversity of Manchester and Christie NHS Foundation Trust, Manchester, United Kingdom. Electronic address: Fiona.Blackhall@christie.nhs.uk. Hopital du Sacre Coeur Montreal, Montreal, Canada. Aix-Marseille University, APHM, INSERM, CNRS, CRCM, Marseille, France. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. Private Medical Institution Euromedservice, St. Petersburg, Pushkin, Russian Federation. Hospital Clinic de Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) Barcelona, Spain. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. KU Leuven, University Hospital Leuven, Leuven, Belgium. National & Kapodistrian University of Athens, Athens, Greece. Odense Universitets Hospital, Odense, Denmark. Krankenhaus Martha-Maria Halle-Doelau Halle, Germany. Oregon Health & Science University, Portland, Oregon, USA. Istituto Nazionale Tumori IRCCS Regina Elena, Roma, Italy. Kyushu University Hospital, Fukuoka, Japan. Hacettepe University, Cancer Institute, Ankara, Turkey. Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. Kanagawa Cancer Center, Yokohama, Japan. University of Groningen and University Medical Center Groningen, Groningen, Netherlands. AbbVie, Inc, North Chicago, Ilinois, USA. Asklepios Fachkliniken München-Gauting, Gauting, Germany.
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AbstractIntroduction: Delta-like protein 3 (DLL3), an atypical Notch ligand, is expressed in small cell lung cancer (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 via a protease-cleavable linker. 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: TAHOE was an open-label, 2:1 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 2 cycles, with 2 additional cycles available to patients who met protocol-defined criteria for continued dosing. Topotecan (1.5 mg/m2) was administered intravenously on Days 1-5 of a 21-day cycle. The primary endpoint was overall survival (OS). Results: Patients randomized to Rova-T (n=296) and topotecan (n=148) were included in efficacy analyses. The median age was 64 years, and 77% had extensive disease at initial diagnosis. Median OS (95% CI) 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% CI: 1.17-1.82]). An independent data monitoring committee recommended that enrollment be discontinued due to 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 showed an inferior OS and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC. Significant unmet therapeutic need remains in this population.
CitationBlackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, et al. 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.
JournalJournal of Thorac Oncology