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Randomized Controlled Trial
. 2021 Sep;16(9):1547-1558.
doi: 10.1016/j.jtho.2021.02.009. Epub 2021 Feb 16.

Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study

Fiona Blackhall  1 , Kevin Jao  2 , Laurent Greillier  3 , Byoung Chul Cho  4 , Konstantin Penkov  5 , Noemi Reguart  6 , Margarita Majem  7 , Kristiaan Nackaerts  8 , Konstantinos Syrigos  9 , Karin Hansen  10 , Wolfgang Schuette  11 , Jeremy Cetnar  12 , Federico Cappuzzo  13 , Isamu Okamoto  14 , Mustafa Erman  15 , Seppo W Langer  16 , Terufumi Kato  17 , Harry Groen  18 , Zhaowen Sun  19 , Yan Luo  19 , Poonam Tanwani  19 , Laura Caffrey  19 , Philip Komarnitsky  19 , Niels Reinmuth  20
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Free article
Randomized Controlled Trial

Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study

Fiona Blackhall et al. J Thorac Oncol. 2021 Sep.
Free article

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.

Keywords: Delta-like protein 3; Rovalpituzumab tesirine; Small cell lung cancer; Topotecan.

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