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RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability

INTRODUCTION: RELAY was a global, double-blind, placebo-controlled phase III study that demonstrated superior progression-free survival (PFS) for ramucirumab plus erlotinib (RAM + ERL) versus placebo plus erlotinib (PBO + ERL) in the first-line treatment of patients with epidermal growth factor rece...

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Autores principales: Nadal, Ernest, Horinouchi, Hidehito, Shih, Jin-Yuan, Nakagawa, Kazuhiko, Reck, Martin, Garon, Edward B., Wei, Yu-Feng, Kollmeier, Jens, Frimodt-Moller, Bente, Barrett, Emily, Lipkovich, Olga, Visseren-Grul, Carla, Novello, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763844/
https://www.ncbi.nlm.nih.gov/pubmed/34928484
http://dx.doi.org/10.1007/s40264-021-01127-2
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author Nadal, Ernest
Horinouchi, Hidehito
Shih, Jin-Yuan
Nakagawa, Kazuhiko
Reck, Martin
Garon, Edward B.
Wei, Yu-Feng
Kollmeier, Jens
Frimodt-Moller, Bente
Barrett, Emily
Lipkovich, Olga
Visseren-Grul, Carla
Novello, Silvia
author_facet Nadal, Ernest
Horinouchi, Hidehito
Shih, Jin-Yuan
Nakagawa, Kazuhiko
Reck, Martin
Garon, Edward B.
Wei, Yu-Feng
Kollmeier, Jens
Frimodt-Moller, Bente
Barrett, Emily
Lipkovich, Olga
Visseren-Grul, Carla
Novello, Silvia
author_sort Nadal, Ernest
collection PubMed
description INTRODUCTION: RELAY was a global, double-blind, placebo-controlled phase III study that demonstrated superior progression-free survival (PFS) for ramucirumab plus erlotinib (RAM + ERL) versus placebo plus erlotinib (PBO + ERL) in the first-line treatment of patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) mutation-positive, metastatic non-small-cell lung cancer (NSCLC). OBJECTIVE: This article provides an in-depth analysis of the safety profile of RAM + ERL versus PBO + ERL observed in RELAY. METHODS: Eligible patients met these criteria: stage IV NSCLC; EGFR exon 19 deletion or exon 21 substitution (L858R) mutation; Eastern Cooperative Oncology Group performance status 0 or 1; and no central nervous system metastases. Patients were randomized (1:1) to receive erlotinib 150 mg/day orally plus either ramucirumab 10 mg/kg intravenously or matching placebo once every 2 weeks, until disease progression or unacceptable toxicity. The primary endpoint was PFS. Safety was evaluated based on reported treatment-emergent adverse events (AEs) and clinical laboratory assessments. RESULTS: The safety population comprised 446 patients (221 in RAM+ERL arm; 225 in PBO + ERL arm) who received at least one dose of study drug between January 2016 and February 2018. The overall incidence of grade ≥ 3 AEs was higher with RAM + ERL than with PBO + ERL, primarily driven by grade 3 hypertension. Grade ≥ 3 dermatitis acneiform and diarrhea were also reported more frequently in the RAM + ERL arm. The increased incidence of AEs with RAM + ERL was easily detected through routine monitoring and managed through dose adjustments and appropriate supportive care. CONCLUSION: This in-depth safety analysis from RELAY supports that RAM + ERL, irrespective of the increased incidence of AEs, does not affect a patient’s ability to benefit from treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT02411448. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40264-021-01127-2.
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spelling pubmed-87638442022-01-31 RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability Nadal, Ernest Horinouchi, Hidehito Shih, Jin-Yuan Nakagawa, Kazuhiko Reck, Martin Garon, Edward B. Wei, Yu-Feng Kollmeier, Jens Frimodt-Moller, Bente Barrett, Emily Lipkovich, Olga Visseren-Grul, Carla Novello, Silvia Drug Saf Original Research Article INTRODUCTION: RELAY was a global, double-blind, placebo-controlled phase III study that demonstrated superior progression-free survival (PFS) for ramucirumab plus erlotinib (RAM + ERL) versus placebo plus erlotinib (PBO + ERL) in the first-line treatment of patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) mutation-positive, metastatic non-small-cell lung cancer (NSCLC). OBJECTIVE: This article provides an in-depth analysis of the safety profile of RAM + ERL versus PBO + ERL observed in RELAY. METHODS: Eligible patients met these criteria: stage IV NSCLC; EGFR exon 19 deletion or exon 21 substitution (L858R) mutation; Eastern Cooperative Oncology Group performance status 0 or 1; and no central nervous system metastases. Patients were randomized (1:1) to receive erlotinib 150 mg/day orally plus either ramucirumab 10 mg/kg intravenously or matching placebo once every 2 weeks, until disease progression or unacceptable toxicity. The primary endpoint was PFS. Safety was evaluated based on reported treatment-emergent adverse events (AEs) and clinical laboratory assessments. RESULTS: The safety population comprised 446 patients (221 in RAM+ERL arm; 225 in PBO + ERL arm) who received at least one dose of study drug between January 2016 and February 2018. The overall incidence of grade ≥ 3 AEs was higher with RAM + ERL than with PBO + ERL, primarily driven by grade 3 hypertension. Grade ≥ 3 dermatitis acneiform and diarrhea were also reported more frequently in the RAM + ERL arm. The increased incidence of AEs with RAM + ERL was easily detected through routine monitoring and managed through dose adjustments and appropriate supportive care. CONCLUSION: This in-depth safety analysis from RELAY supports that RAM + ERL, irrespective of the increased incidence of AEs, does not affect a patient’s ability to benefit from treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT02411448. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40264-021-01127-2. Springer International Publishing 2021-12-20 2022 /pmc/articles/PMC8763844/ /pubmed/34928484 http://dx.doi.org/10.1007/s40264-021-01127-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research Article
Nadal, Ernest
Horinouchi, Hidehito
Shih, Jin-Yuan
Nakagawa, Kazuhiko
Reck, Martin
Garon, Edward B.
Wei, Yu-Feng
Kollmeier, Jens
Frimodt-Moller, Bente
Barrett, Emily
Lipkovich, Olga
Visseren-Grul, Carla
Novello, Silvia
RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability
title RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability
title_full RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability
title_fullStr RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability
title_full_unstemmed RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability
title_short RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability
title_sort relay, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, epidermal growth factor receptor mutation-positive, metastatic non-small-cell lung cancer: safety profile and manageability
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763844/
https://www.ncbi.nlm.nih.gov/pubmed/34928484
http://dx.doi.org/10.1007/s40264-021-01127-2
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