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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.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: A placebo-controlled, phase II trial of erlotinib + onartuzumab, a humanized monovalent antibody to the MET receptor, demonstrated a benefit in progression-free survival (PFS) when compared with erlotinib in patients with MET-positive NSCLC (JCO 2013;31;4105). The aim of the METLung trial was to confirm the efficacy and safety of onartuzumab + erlotinib in MET-positive NSCLC. Methods: This prospective, randomized, double-blind, placebo-controlled trial enrolled patients with previously treated MET-positive stage IIIb/IV NSCLC. MET diagnostic status was determined by an immunohistochemistry (IHC) assay using the CONFIRM anti-total MET SP44 monoclonal antibody (Ventana). Eligibility criteria included: ECOG PS 0–1, 1–2 prior lines of chemotherapy, and normal organ function. Stratification factors: EGFR mutation status (activating mutation vs negative; cobas® EGFR assay), MET IHC (2+ vs 3+), number of prior treatments (1 vs 2), and histology (squamous vs non-squamous). Patients were randomized (1:1) to receive erlotinib 150mg PO daily + placebo or onartuzumab 15mg/kg IV every 21 days. Tumor assessments occurred every 6 weeks. The primary endpoint was overall survival (OS). The sample size (n=490) was based on the assumption that adding onartuzumab to erlotinib would improve OS by 41% with 90% power (one-sided alpha 0.025). An interim analysis was planned when 67% (244 events) of the final events were reached. Results: 499 patients were enrolled between Jan 2012 and Aug 2013. An independent data review committee recommended to stop the trial for futility, as the addition of onartuzumab to erlotinib did not improve OS (HR 1.27, p=0.068; median OS 6.8 mos vs 9.1 mos), PFS (HR 0.99, p=0.92; median PFS 2.7 mos vs 2.6 mos), or overall response rate (8.4% vs 9.6%; p=0.63). The most frequent adverse events that were higher in the combination arm were peripheral edema, hypoalbuminemia, back pain, dyspnea, nausea, acneiform dermatitis, and rash. Conclusions: The phase III study did not confirm the efficacy results observed in the phase II study. Exploratory analyses based on molecular subgroups are pending. Clinical trial information: NCT01456325.
Abstracts by David R. Spigel:
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