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Randomized phase II trial of Onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer.


ABSTRACT:

Purpose

Increased hepatocyte growth factor/MET signaling is associated with poor prognosis and acquired resistance to epidermal growth factor receptor (EGFR) -targeted drugs in patients with non-small-cell lung cancer (NSCLC). We investigated whether dual inhibition of MET/EGFR results in clinical benefit in patients with NSCLC.

Patients and methods

Patients with recurrent NSCLC were randomly assigned at a ratio of one to one to receive onartuzumab plus erlotinib or placebo plus erlotinib; crossover was allowed at progression. Tumor tissue was required to assess MET status by immunohistochemistry (IHC). Coprimary end points were progression-free survival (PFS) in the intent-to-treat (ITT) and MET-positive (MET IHC diagnostic positive) populations; additional end points included overall survival (OS), objective response rate, and safety.

Results

There was no improvement in PFS or OS in the ITT population (n = 137; PFS hazard ratio [HR], 1.09; P = .69; OS HR, 0.80; P = .34). MET-positive patients (n = 66) treated with erlotinib plus onartuzumab showed improvement in both PFS (HR, .53; P = .04) and OS (HR, .37; P = .002). Conversely, clinical outcomes were worse in MET-negative patients treated with onartuzumab plus erlotinib (n = 62; PFS HR, 1.82; P = .05; OS HR, 1.78; P = .16). MET-positive control patients had worse outcomes versus MET-negative control patients (n = 62; PFS HR, 1.71; P = .06; OS HR, 2.61; P = .004). Incidence of peripheral edema was increased in onartuzumab-treated patients.

Conclusion

Onartuzumab plus erlotinib was associated with improved PFS and OS in the MET-positive population. These results combined with the worse outcomes observed in MET-negative patients treated with onartuzumab highlight the importance of diagnostic testing in drug development.

SUBMITTER: Spigel DR 

PROVIDER: S-EPMC4878106 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Randomized phase II trial of Onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer.

Spigel David R DR   Ervin Thomas J TJ   Ramlau Rodryg A RA   Daniel Davey B DB   Goldschmidt Jerome H JH   Blumenschein George R GR   Krzakowski Maciej J MJ   Robinet Gilles G   Godbert Benoit B   Barlesi Fabrice F   Govindan Ramaswamy R   Patel Taral T   Orlov Sergey V SV   Wertheim Michael S MS   Yu Wei W   Zha Jiping J   Yauch Robert L RL   Patel Premal H PH   Phan See-Chun SC   Peterson Amy C AC  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20131007 32


<h4>Purpose</h4>Increased hepatocyte growth factor/MET signaling is associated with poor prognosis and acquired resistance to epidermal growth factor receptor (EGFR) -targeted drugs in patients with non-small-cell lung cancer (NSCLC). We investigated whether dual inhibition of MET/EGFR results in clinical benefit in patients with NSCLC.<h4>Patients and methods</h4>Patients with recurrent NSCLC were randomly assigned at a ratio of one to one to receive onartuzumab plus erlotinib or placebo plus e  ...[more]

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