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 |
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Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
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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. |
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ISSN: | 0007-0920 1532-1827 |
DOI: | 10.1038/bjc.2017.226 |