1. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study
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Ilié, Marius, Mazières, Julien, Chamorey, Emmanuel, Heeke, Simon, Benzaquen, Jonathan, Thamphya, Brice, Boutros, Jacques, Tiotiu, Angélica, Fayada, Julien, Cadranel, Jacques, Poudenx, Michel, Moro-Sibilot, Denis, Barlesi, Fabrice, Thariat, Juliette, Clément-Duchêne, Christelle, Tomasini, Pascale, Hofman, Véronique, Marquette, Charles-Hugo, Hofman, Paul, Israel-Biet, Dominique, Pison, Christophe, Lantuejoul, Sylvie, Stephanov, Olivier, Juliette, Meyzenc, Mendozat, Christophe, Zaidi, Manel, Coulouvrat, Sandra, Col, Edwige, Chanez, Pascal, Greillier, Laurent, Mascaux, Céline, Jourdan, Sandrine, Roger, Aurélie, Biemar, Julie, Randriamampionona, Rondro, Chabot, François, Vignaud, Jean-Michel, Lacomme, Stéphanie, Lomazzi, Sandra, Laurent, Carine, Bulsei, Xavier, Bischoff, Laura, Rakotonirina, Raymond, Layouni, Mehdi, Deslee, Gaëtan, Mal, Hervé, Kessler, Romain, Vergnon, Jean-Michel, Pelissier, Isabelle, Cuvelier, Antoine, Bourdin, Arnaud, Jounieaux, Vincent, Roche, Nicolas, Jouneau, Stéphane, Bonniaud, Philippe, Scherpereel, Arnaud, Mornex, Jean François, Steenhouwer, François, Leroy, Sylvie, Marquette, Charles Hugo, Mazzette, Andrea, Padovani, Bernard, Long-Mira, Elodie, Lassalle, Sandra, Pradelli, Johanna, Martinez, Estelle, Habault, Marine, Bonnard, Mélanie, Moutarde, Julie, Yatimi, Rachida, Labsi, Hakima, Gazoppi, Loïc, Lpce, Tumorothèque, Griffonnet, Jennifer, Fontaine, Maureen, Guillemart, Ariane, Butori, Catherine, Selva, Eric, Otto, Josiane, Hebert, Christophe, Botchiellini, Delphine, Boudouf, Soukaina, Menier, Margaux, Occeli, Estelle, Bellentani, Sophie, Pion, Carine, Fournier, Elodie, Gervais, Radj, Hamond, Karim, Marchand-Adam, Sylvain, Plantier, Laurent, Fajolle, Gaelle, Rayez, Mélanie, Fallet, Vincent, Wislez, Marie, Antoine, Martine, Cote, Jean-François, Chaabane, Nouha, Ruppert, Anne Marie, Bertrand, Eliane, Rodenas, Anita, Pontdeme, Gwenaëlle, Mathiot, Nathalie, Ribert, Tamazouzt, Guibert, Nicolas, Rouviere, Damien, Bousquet, Emilie, Bigay-Game, Laurence, Hermant, Christophe, Plat, Gavin, Rouquette, Isabelle, Evrard, Solène, Gouin, Sandrine, Clermont, Estelle Taranchon, Dormoy, Inge, Coulomb, Christelle, Pradine, Anne, Lambert, Véronique, Laborde, Lilian, Castelnau, Olivier, University of Manchester [Manchester], Hôpital du Sacré-Coeur de Montréal, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Yonsei University College of Medicine [Séoul, Corée du Sud], August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain], Hospital de la Santa Creu i Sant Pau, University Hospitals Leuven [Leuven], National and Kapodistrian University of Athens (NKUA), Odense University Hospital (OUH), Oregon Health and Science University [Portland] (OHSU), Kyushu University, Hacettepe University = Hacettepe Üniversitesi, University of Copenhagen = Københavns Universitet (UCPH), University of Groningen [Groningen], Abbvie Inc. [North Chicago], Asklepios Klinikum Uckermark GmbH, Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,CELL LUNG-CANCER ,Population ,Peripheral edema ,Phases of clinical research ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Delta-like protein 3 ,Rovalpituzumab tesirine ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,DRUG ,education ,ComputingMilieux_MISCELLANEOUS ,Chemotherapy ,education.field_of_study ,Small cell lung cancer ,business.industry ,Hazard ratio ,Confidence interval ,030104 developmental biology ,030220 oncology & carcinogenesis ,Topotecan ,medicine.symptom ,business ,medicine.drug - 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. ispartof: JOURNAL OF THORACIC ONCOLOGY vol:16 issue:9 pages:1547-1558 ispartof: location:United States status: published
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- 2021
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