Details

Autor(en) / Beteiligte

• SPIGEL, David R
• ERVIN, Thomas J
• GOVINDAN, Ramaswamy
• PATEL, Taral
• ORLOV, Sergey V
• WERTHEIM, Michael S
• WEI YU
• JIPING ZHA
• YAUCH, Robert L
• PATEL, Premal H
• PHAN, See-Chun
• PETERSON, Amy C
• RAMLAU, Rodryg A
• DANIEL, Davey B
• GOLDSCHMIDT, Jerome H
• BLUMENSCHEIN, George R
• KRZAKOWSKI, Maciej J
• ROBINET, Gilles
• GODBERT, Benoit
• BARLESI, Fabrice

Titel

Randomized Phase II Trial of Onartuzumab in Combination With Erlotinib in Patients With Advanced Non–Small-Cell Lung Cancer

Ist Teil von

• Journal of clinical oncology, 2013-11, Vol.31 (32), p.4105-4114

Ort / Verlag

Alexandria, VA: American Society of Clinical Oncology

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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. 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. 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.