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Clinical Trial
. 2017 Sep 5;117(6):757-766.
doi: 10.1038/bjc.2017.226. Epub 2017 Aug 3.

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

Tudor-Eliade Ciuleanu  1 , Samreen Ahmed  2 , Joo-Hang Kim  3 , Jörg Mezger  4 , Keunchil Park  5 , Michael Thomas  6 , Jihong Chen  7 , Srinivasu Poondru  7 , Jan M VanTornout  7 , Debbie Whitcomb  7 , Fiona Blackhall  8
Affiliations
Clinical Trial

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

Tudor-Eliade Ciuleanu et al. Br J Cancer. .

Abstract

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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Conflict of interest statement

Tudor-Eliade Ciuleanu has served on an advisory board for Astellas, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Merck, Merck Sharp and Dohme, Pfizer, Roche, and Boehringer Ingelheim. JHK declares grant funding from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, and Roche. KP has served in an advisory role for Astellas and Roche. JC, SP, JMV, and DW were employed with Astellas at the time of the study. SA, JM, MT, and FB have no conflicts to disclose.

Figures

Figure 1
Figure 1
Progression-free survival (A) and overall survival (B), full analysis set. CI=confidence interval; HR=hazard ratio.
See this image and copyright information in PMC

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