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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Veröffentlicht in:British journal of cancer 2017-09, Vol.117 (6), p.757-766
Hauptverfasser: 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
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Sprache:eng
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Zusammenfassung: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2017.226