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
