%0 Journal Article
%A Johnson, Melissa L
%A Zvirbule, Zanete
%A Laktionov, Konstantin
%A Helland, Aslaug
%A Cho, Byoung Chul
%A Gutierrez, Vanesa
%A Colinet, Benoît
%A Lena, Herve
%A Wolf, Martin
%A Gottfried, Maya
%A Okamoto, Isamu
%A van der Leest, Cor
%A Rich, Patricia
%A Hung, Jen-Yu
%A Appenzeller, Christina
%A Sun, Zhaowen
%A Maag, David
%A Luo, Yan
%A Nickner, Caroline
%A Vajikova, Alena
%A Komarnitsky, Philip
%A Bar, Jair
%T Rovalpituzumab Tesirine as a Maintenance Therapy After First-Line Platinum-Based Chemotherapy in Patients With Extensive-Stage-SCLC: Results From the Phase 3 MERU Study.
%D 2021
%U http://hdl.handle.net/10668/17534
%X Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, an atypical Notch ligand expressed in SCLC tumors. We evaluated the efficacy of Rova-T versus placebo as maintenance therapy in patients with extensive-stage-SCLC after platinum-based chemotherapy. MERU was a phase 3 randomized, double-blinded, placebo-controlled study. Patients without disease progression after four cycles of platinum-based, front-line chemotherapy were randomized in a 1:1 ratio to receive 0.3 mg/kg Rova-T or placebo (every 6 wk, omitted every third cycle). Primary efficacy end points were progression-free survival (PFS) evaluated by the Central Radiographic Assessment Committee and overall survival (OS) in patients with DLL3-high tumors. Median age of all randomized patients (N = 748) was 64 years; 78% had TNM stage IV disease. At futility analysis of the subset with DLL3-high tumors, the hazard ratio for OS was 1.07 (95% confidence interval: 0.84-1.36) favoring the placebo arm, with median OS of 8.5 and 9.8 months in the Rova-T and placebo arms, respectively; futility criteria were met. Rova-T significantly improved PFS versus placebo by investigator assessment (4.0 versus 1.4 mo, hazard ratio = 0.48, p  Because of the lack of survival benefit in the Rova-T arm, the study did not meet its primary end point and was terminated early. As a result, the Central Radiographic Assessment Committee evaluation of PFS was not performed. The frequency of grade greater than or equal to 3 and drug-related toxicities were higher with Rova-T versus placebo. Rova-T was associated with unique toxicities, such as pleural and pericardial effusions, photosensitivity reaction, and peripheral edema, which should be carefully considered in the population with extensive-stage-SCLC.
%K DLL3
%K Maintenance
%K Phase 3
%K Platinum-based chemotherapy
%K Rovalpituzumab tesirine
%K Small cell lung cancer
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