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
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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. / Blackhall, Fiona; Jao, Kevin; Greillier, Laurent; Cho, Byoung Chul; Penkov, Konstantin; Reguart, Noemi; Majem, Margarita; Nackaerts, Kristiaan; Syrigos, Konstantinos; Hansen, Karin; Schuette, Wolfgang; Cetnar, Jeremy; Cappuzzo, Federico; Okamoto, Isamu; Erman, Mustafa; Langer, Seppo W; Kato, Terufumi; Groen, Harry; Sun, Zhaowen; Luo, Yan; Tanwani, Poonam; Caffrey, Laura; Komarnitsky, Philip; Reinmuth, Niels.
In: Journal of Thoracic Oncology, Vol. 16, No. 9, 2021, p. 1547-1558.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Efficacy and Safety of Rovalpituzumab Tesirine Compared with Topotecan as Second-Line Therapy in DLL3-High Small Cell Lung Cancer
T2 - Results from the Phase 3 TAHOE Study
AU - Blackhall, Fiona
AU - Jao, Kevin
AU - Greillier, Laurent
AU - Cho, Byoung Chul
AU - Penkov, Konstantin
AU - Reguart, Noemi
AU - Majem, Margarita
AU - Nackaerts, Kristiaan
AU - Syrigos, Konstantinos
AU - Hansen, Karin
AU - Schuette, Wolfgang
AU - Cetnar, Jeremy
AU - Cappuzzo, Federico
AU - Okamoto, Isamu
AU - Erman, Mustafa
AU - Langer, Seppo W
AU - Kato, Terufumi
AU - Groen, Harry
AU - Sun, Zhaowen
AU - Luo, Yan
AU - Tanwani, Poonam
AU - Caffrey, Laura
AU - Komarnitsky, Philip
AU - Reinmuth, Niels
N1 - Copyright © 2021. Published by Elsevier Inc.
PY - 2021
Y1 - 2021
N2 - INTRODUCTION: 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.
AB - INTRODUCTION: 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.
U2 - 10.1016/j.jtho.2021.02.009
DO - 10.1016/j.jtho.2021.02.009
M3 - Journal article
C2 - 33607312
VL - 16
SP - 1547
EP - 1558
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 9
ER -
ID: 257374197