Publikation

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

Wissenschaftlicher Artikel/Review - 03.04.2021

Bereiche
PubMed
DOI

Zitation
Johnson M, Rich P, Hung J, Appenzeller C, Sun Z, Maag D, Luo Y, Nickner C, Vajikova A, Komarnitsky P, van der Leest C, Okamoto I, Zvirbule Z, Laktionov K, Helland A, Cho B, Gutierrez V, Colinet B, Lena H, Wolf M, Gottfried M, Bar J. 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. J Thorac Oncol 2021; 16:1570-1581.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
J Thorac Oncol 2021; 16
Veröffentlichungsdatum
03.04.2021
eISSN (Online)
1556-1380
Seiten
1570-1581
Kurzbeschreibung/Zielsetzung

INTRODUCTION
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.

METHODS
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.

RESULTS
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 < 0.001). Any-grade adverse events (≥20%) in the Rova-T arm were pleural effusion (27%), decreased appetite (27%), peripheral edema (26%), photosensitivity reaction (25%), fatigue (25%), nausea (22%), and dyspnea (21%).

CONCLUSIONS
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.