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Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer

BACKGROUND: Maintenance therapy is important in advanced/metastatic non-small cell lung cancer (NSCLC). Erlotinib as switch maintenance following platinum-based chemotherapy increases survival. Cross-talk between the epidermal growth factor receptor and insulin-like growth factor receptor (IGFR) pat...

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Autores principales: Ciuleanu, Tudor-Eliade, Ahmed, Samreen, Kim, Joo-Hang, Mezger, Jörg, Park, Keunchil, Thomas, Michael, Chen, Jihong, Poondru, Srinivasu, VanTornout, Jan M, Whitcomb, Debbie, Blackhall, Fiona
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589984/
https://www.ncbi.nlm.nih.gov/pubmed/28772281
http://dx.doi.org/10.1038/bjc.2017.226
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author Ciuleanu, Tudor-Eliade
Ahmed, Samreen
Kim, Joo-Hang
Mezger, Jörg
Park, Keunchil
Thomas, Michael
Chen, Jihong
Poondru, Srinivasu
VanTornout, Jan M
Whitcomb, Debbie
Blackhall, Fiona
author_facet Ciuleanu, Tudor-Eliade
Ahmed, Samreen
Kim, Joo-Hang
Mezger, Jörg
Park, Keunchil
Thomas, Michael
Chen, Jihong
Poondru, Srinivasu
VanTornout, Jan M
Whitcomb, Debbie
Blackhall, Fiona
author_sort Ciuleanu, Tudor-Eliade
collection PubMed
description BACKGROUND: Maintenance therapy is important in advanced/metastatic non-small cell lung cancer (NSCLC). Erlotinib as switch maintenance following platinum-based chemotherapy increases survival. Cross-talk between the epidermal growth factor receptor and insulin-like growth factor receptor (IGFR) pathways mediate resistance to individual receptor blockade. This study compared maintenance linsitinib plus erlotinib vs erlotinib plus placebo in patients with NSCLC. METHODS: In this Phase II randomised trial, patients without progression following four cycles of first-line platinum-based chemotherapy (N=205) received continuous schedule maintenance oral linsitinib 150 mg or placebo BID combined with erlotinib 150 mg QD for 21-day cycles. The primary endpoint was progression-free survival (PFS). RESULTS: The study was unblinded early due to linsitinib non-superiority. No difference was found between the two treatment groups in median PFS of 125 days linsitinib vs 129 days placebo (P=0.601); no difference in overall survival (OS) was observed. Tolerability was similar, although in the linsitinib group, treatment-related adverse events and discontinuations were more frequent. No drug–drug interaction was implicated. CONCLUSIONS: Linsitinib maintenance therapy added to erlotinib did not improve PFS or OS in non-progressing NSCLC patients. This highlights the need for robust biomarkers of response for combinations that incorporate IGFR-targeted therapies in maintenance or other therapeutic settings.
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spelling pubmed-55899842018-09-05 Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer Ciuleanu, Tudor-Eliade Ahmed, Samreen Kim, Joo-Hang Mezger, Jörg Park, Keunchil Thomas, Michael Chen, Jihong Poondru, Srinivasu VanTornout, Jan M Whitcomb, Debbie Blackhall, Fiona Br J Cancer Clinical Study BACKGROUND: Maintenance therapy is important in advanced/metastatic non-small cell lung cancer (NSCLC). Erlotinib as switch maintenance following platinum-based chemotherapy increases survival. Cross-talk between the epidermal growth factor receptor and insulin-like growth factor receptor (IGFR) pathways mediate resistance to individual receptor blockade. This study compared maintenance linsitinib plus erlotinib vs erlotinib plus placebo in patients with NSCLC. METHODS: In this Phase II randomised trial, patients without progression following four cycles of first-line platinum-based chemotherapy (N=205) received continuous schedule maintenance oral linsitinib 150 mg or placebo BID combined with erlotinib 150 mg QD for 21-day cycles. The primary endpoint was progression-free survival (PFS). RESULTS: The study was unblinded early due to linsitinib non-superiority. No difference was found between the two treatment groups in median PFS of 125 days linsitinib vs 129 days placebo (P=0.601); no difference in overall survival (OS) was observed. Tolerability was similar, although in the linsitinib group, treatment-related adverse events and discontinuations were more frequent. No drug–drug interaction was implicated. CONCLUSIONS: Linsitinib maintenance therapy added to erlotinib did not improve PFS or OS in non-progressing NSCLC patients. This highlights the need for robust biomarkers of response for combinations that incorporate IGFR-targeted therapies in maintenance or other therapeutic settings. Nature Publishing Group 2017-09-05 2017-08-03 /pmc/articles/PMC5589984/ /pubmed/28772281 http://dx.doi.org/10.1038/bjc.2017.226 Text en Copyright © 2017 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Clinical Study
Ciuleanu, Tudor-Eliade
Ahmed, Samreen
Kim, Joo-Hang
Mezger, Jörg
Park, Keunchil
Thomas, Michael
Chen, Jihong
Poondru, Srinivasu
VanTornout, Jan M
Whitcomb, Debbie
Blackhall, Fiona
Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer
title Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer
title_full Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer
title_fullStr Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer
title_full_unstemmed Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer
title_short Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer
title_sort randomised phase 2 study of maintenance linsitinib (osi-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589984/
https://www.ncbi.nlm.nih.gov/pubmed/28772281
http://dx.doi.org/10.1038/bjc.2017.226
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