Onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIb or IV NSCLC: Results from the pivotal phase III randomized, multicenter, placebo-controlled METLung (OAM4971g) global trial.

MET/HGF targeted drugs as potential therapeutic strategies in non-small cell lung cancer

“…Two phase III studies were designed to confirm these results (NCT01456325, NCT01887886) [128,129]. The first, which enrolled 499 patients, failed to confirm the benefit of onartuzumab plus erlotinib in EGFR-mutated patients with high MET expression in either OS (6.8 months vs 9.1 months; HR=1.27; p=0.068), PFS (2.7 months vs. 2.6 months; HR=0.99; p=0.92), or ORR (8.4% vs 9.6%; p=0.63) [129]. The second is phase is currently recruiting participants.…”

c-MET-mediated resistance to EGFR inhibitors in head and neck cancer: How to move from bench to bedside

“…As seen in Table 1, most studies were conducted in lung cancer evaluating tivantinib, an oral small-molecule c-MET inhibitor, or onartuzumab, a humanized monoclonal anti-c-MET antibody. However, when looking at the outcomes from a wider perspective, a trend towards improved response rate (5 out of 8 trials), progression-free (5/8), and overall survivals (6/8) is evident with the MARQUEE trial demonstrating, as the only one, statistically significant differences in overall response rate and median progression-free survival [12][13][14][15][16][17][18][19]. Taken together, the findings indicate a promising biological activity delivered by these molecularly targeted doublets.…”

“…Three trials (Spigel, 2013;Scagliotti, 2015;Eng, 2016) suggested a potential survival advantage in patients with c-MET-high status by immunohistochemistry [13,15,19]. Unfortunately, a large phase III trial evaluating the addition of tivantinib to erlotinib in pretreated c-MET positive non-small-cell lung cancer cases did not confirm this assumption [14]. Nevertheless, in the era of personalized medicine, adoption of biomarker-based patient stratification is essential and failure to do so may undesirably mask clinical benefits.…”

The use of biomarkers in the treatment of non-small cell lung cancer

“…A phase III study evaluating the use of onartuzumab, a monoclonal antibody directed against the MET receptor, in combination with erlotinib to treat patients with MET amplification or overexpression failed to demonstrate meaningful efficacy, despite promising results in a phase II study. [40] A more promising strategy is utilizing small molecule tyrosine kinase inhibitors of MET. In a phase 1 study, 16 patients with MET amplified NSCLC as assessed by FISH were treated with crizotinib and preliminary results demonstrated partial response in 4 of 12 patients who were evaluable for response.…”