Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study
Por:
Blackhall, F, Jao, K, Greillier, L, Cho, BC, Penkov, K, Reguart, N, Majem, M, Nackaerts, K, Syrigos, K, Hansen, K, Schuette, W, Cetnar, J, Cappuzzo, F, Okamoto, I, Erman, M, Langer, SW, Kato, T, Groen, H, Sun, ZW, Luo, Y, Tanwani, P, Caffrey, L, Komarnitsky, P, Reinmuth, N
Publicada:
1 sep 2021
Ahead of Print:
1 ago 2021
Resumen:
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.
Filiaciones:
Blackhall, F:
Univ Manchester, Div Canc Sci, Manchester, Lancs, England
Christie Natl Hlth Serv NHS Fdn Trust, Dept Med Oncol, Wilmslow Rd, Manchester M20 4BX, Lancs, England
Greillier, L:
Hop Sacre Coeur Montreal, Dept Hematol & Oncol, Montreal, PQ, Canada
AixMarseille Univ, Assistance Publ Hop Marseille APHM, Inst Natl Sante & Rech Med INSERM,Multidisciplina, Ctr Natl Rech Sci CNRS,Ctr Rech Cancerol Marseill, Marseille, France
Cho, BC:
Yonsei Univ, Coll Med, Yonsei Canc Ctr, Div Med Oncol,Dept Internal Med, Seoul, South Korea
Penkov, K:
Private Med Inst Euromedservice, St Petersburg, Russia
Reguart, N:
Hosp Clin Barcelona, August Pi i Sunyer Biomed Res Inst IDIBAPS, Dept Med Oncol, Barcelona, Spain
Majem, M:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona, Spain
Nackaerts, K:
Katholieke Univ KU Leuven, Univ Hosp Leuven, Dept Pulmonol & Resp Oncol, Leuven, Belgium
Syrigos, K:
Natl & Kapodistrian Univ Athens, Dept Med, Athens, Greece
Hansen, K:
Odense Univ Hosp, Dept Oncol, Odense, Denmark
Schuette, W:
Krankenhaus Martha Maria Halle Doelau, Med Dept 2, Halle, Germany
Cetnar, J:
Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA
Cappuzzo, F:
Ist Nazl Tumori Ist Ricovero & Cura Carattere Sci, Dept Med Oncol, Rome, Italy
Okamoto, I:
Kyushu Univ Hosp, Dept Med Oncol, Fukuoka, Japan
Erman, M:
Hacettepe Univ, Inst Canc, Dept Med Oncol, Ankara, Turkey
Langer, SW:
Univ Copenhagen, Rigshosp, Copenhagen, Denmark
Kato, T:
Kanagawa Canc Ctr, Dept Thorac Oncol, Yokohama, Kanagawa, Japan
Groen, H:
Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Dis, Groningen, Netherlands
Sun, ZW:
AbbVie Inc, N Chicago, IL USA
Luo, Y:
AbbVie Inc, N Chicago, IL USA
Tanwani, P:
AbbVie Inc, N Chicago, IL USA
Caffrey, L:
AbbVie Inc, N Chicago, IL USA
Komarnitsky, P:
AbbVie Inc, N Chicago, IL USA
Reinmuth, N:
Asklepios Fachkliniken Munchen Gauting, Thorac Oncol Dept, Gauting, Germany
Green Submitted, Green Published, hybrid
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