AI Article Synopsis
- The phase II JO28638 study aimed to assess the combination of onartuzumab and erlotinib in treating advanced, MET-positive non-small-cell lung cancer (NSCLC) with EGFR mutations but was halted due to findings from another study showing it was ineffective.
- A total of 61 chemotherapy-naïve patients participated, demonstrating a median progression-free survival of 8.5 months and an overall response rate of 68.9%, but all experienced adverse events, leading to 26 patients discontinuing treatment.
- The findings are considered inconclusive as the study ended prematurely, preventing a definitive understanding of the treatment's efficacy and safety.
Article Abstract
Introduction: The phase II JO28638 study evaluated first-line onartuzumab plus erlotinib in patients with MET-positive advanced, metastatic, or post-operative recurrent non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The study was stopped following termination of the global METLung study (OAM4971g), which showed lack of efficacy in the onartuzumab/erlotinib arm. We present immature efficacy and safety data from JO28638.
Materials And Methods: Chemotherapy-naïve patients aged ≥ 20 years were enrolled. Patients received onartuzumab (15 mg/kg every 3 weeks) plus erlotinib (150 mg once daily) until progression or unacceptable toxicity. The co-primary endpoints were investigator (INV)-assessed progression-free survival (PFS) and safety. Secondary endpoints: overall response rate (ORR), disease control rate (DCR), overall survival (OS), duration of response (DOR), and pharmacokinetics. Exploratory biomarker analyses were also conducted.
Results: 61 patients received treatment. Median age was 67 years and most patients had stage IV NSCLC (71%), MET-IHC score 2 (87%), and exon 19 deletion EGFR mutation (53%). Median PFS (INV) was 8.5 months (95% confidence interval [CI] 6.8-12.4); median OS was 15.6 months (95% CI 15.6-not evaluable); ORR was 68.9% (95% CI 55.7-80.1); median DOR was not reached; DCR was 88.5% (95% CI 77.8-95.3). Pharmacokinetics were similar to previous studies. All patients experienced an adverse event (AE); 26 patients discontinued treatment due to AEs; no grade 5 AEs were reported. No significant correlation was found between biomarkers and efficacy outcomes.
Conclusion: The results presented are inconclusive due to the early termination of the study.
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Article Synopsis
- The phase II JO28638 study aimed to assess the combination of onartuzumab and erlotinib in treating advanced, MET-positive non-small-cell lung cancer (NSCLC) with EGFR mutations but was halted due to findings from another study showing it was ineffective.
- A total of 61 chemotherapy-naïve patients participated, demonstrating a median progression-free survival of 8.5 months and an overall response rate of 68.9%, but all experienced adverse events, leading to 26 patients discontinuing treatment.
- The findings are considered inconclusive as the study ended prematurely, preventing a definitive understanding of the treatment's efficacy and safety.
Background: Dysregulated hepatocyte growth factor/mesenchymal-epithelial transition (MET) signaling is associated with poor prognosis and resistance to vascular endothelial growth factor inhibition in metastatic colorectal cancer (mCRC). We report outcomes from a double-blind, multicenter phase II trial of the MET inhibitor onartuzumab in combination with mFOLFOX-6 and bevacizumab for mCRC (GO27827; NCT01418222).
Materials And Methods: Patients were randomized 1:1 to receive onartuzumab (10 mg/kg intravenously [IV]) or placebo plus mFOLFOX-6 and bevacizumab (5 mg/kg IV).
Importance: Dysregulation of the mesenchymal-epithelial transition (MET) signaling pathway is associated with poor prognosis in gastroesophageal adenocarcinoma (GEC). We report results of METGastric, a phase 3 trial of the MET inhibitor onartuzumab plus standard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, MET-positive, advanced GEC.
Objective: To determine whether the addition of onartuzumab to first-line fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) improves efficacy compared with mFOLFOX6 plus placebo in HER2-negative, MET-positive GEC.
Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non-Small-Cell Lung Cancer.
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Department of Oncology, AOU San Luigi-Orbassano, University of Turin, Turin, Italy.
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