Is Adding Onartuzumab to Erlotinib of Benefit in Advanced Non–Small Cell Lung Cancer?


Key Points

  • No benefit was observed by adding onartuzumab to erlotinib in patients with advanced MET-positive NSCLC who had progressed after platinum-based treatment.
  • A trend toward a detrimental effect was observed in patients with EGFR mutation.

In a phase III METLung trial reported in the Journal of Clinical Oncology, Spigel et al found that adding the MET inhibitor onartuzumab to erlotinib (Tarceva) was of no benefit in patients with MET-positive advanced non–small cell lung cancer (NSCLC) who had progressed after platinum-based treatment. Onartuzumab binds to MET, blocking interaction with hepatocyte growth factor.

Study Details

In the double-blind trial, results of which were first reported in 2014, 499 patients with stage IIIB to IV locally advanced or metastatic NSCLC determined to be MET-positive (≥ 50% of tumor cells with immunohistochemistry scores of moderate or strong) were randomized to receive intravenous onartuzumab at 15 mg/kg on day 1 of each 21-day cycle plus daily erlotinib at 150 mg (n = 250) or intravenous placebo plus daily erlotinib at 150 mg (n = 249). The primary endpoint was overall survival in the intent-to-treat population.

Key Findings

Median duration of follow-up was 7.6 months in the onartuzumab group and 8.0 months in the placebo group. Median overall survival was 6.8 months in the onartuzumab group vs 9.1 months in the placebo group (stratified hazard ratio [HR] = 1.27, P = .067); 52% vs 46% of patients died. Median progression-free survival was 2.7 vs 2.6 months (stratified HR = 0.99, P = .92). Overall response rate was 8.4% vs 9.6%. No benefit of onartuzumab was found in exploratory analyses using MET fluorescence in situ hybridization status and gene expression. Among patients with epidermal growth factor receptor (EGFR) mutation, onartuzumab was associated with a trend toward a detrimental effect on overall survival (HR = 4.68, 95% CI = 0.97–22.63).

Grade 3 to 5 adverse events occurred in 56.0% of the onartuzumab group and 51.2% of the placebo group. Serious adverse events occurred in 33.9% and 30.7%, respectively.

The investigators concluded: “Onartuzumab plus erlotinib did not improve clinical outcomes, with shorter [overall survival] in the onartuzumab arm, compared with erlotinib in patients with MET-positive non–small-cell lung cancer.”

The study was supported by F. Hoffmann La-Roche.

David R. Spigel, MD, of Sarah Cannon Research Institute, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.