A Randomized, Open-Label Phase II Study Evaluating Emibetuzumab Plus Erlotinib and Emibetuzumab Monotherapy in MET Immunohistochemistry Positive NSCLC Patients with Acquired Resistance to Erlotinib.

Autor: Camidge DR; University of Colorado Cancer Center, Denver, CO. Electronic address: Ross.camidge@ucdenver.edu., Moran T; Medical Oncology Department, Catalan Institute of Oncology, Badalona, Spain; Hospital Germans Trias i Pujol, Badalona, Spain; Universitat Autòmoma de Barcelona (UAB), Department of Medicine, Barcelona, Spain; Badalona-Applied Research Group in Oncology (B-ARGO), Barcelona, Spain; Fundació Institut Germans Trias i Pujol (IGTP), Barcelona, Spain., Demedts I; AZ Delta, Roeselare, Belgium., Grosch H; Thorax Klinik Heidelberg, Heidelberg, Germany., Mileham K; Levine Cancer Institute, Charlotte, NC., Molina J; Mayo Clinic, Rochester, MN., Juan-Vidal O; Hospital Universitari i Politécnic La Fe, Valencia, Spain., Bepler G; Karmanos Cancer Institute, Detroit, MI., Goldman JW; David Geffen School of Medicine at UCLA, Los Angeles, CA., Park K; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Wallin J; Eli Lilly and Company, Indianapolis, IN., Wijayawardana SR; Eli Lilly and Company, Indianapolis, IN., Wang XA; Eli Lilly and Company, Indianapolis, IN., Wacheck V; Eli Lilly and Company, Indianapolis, IN., Smit E; VU University Medical Centre, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Clinical lung cancer [Clin Lung Cancer] 2022 Jun; Vol. 23 (4), pp. 300-310. Date of Electronic Publication: 2022 Mar 17.
DOI: 10.1016/j.cllc.2022.03.003
Abstrakt: Introduction: The hepatocyte growth factor receptor MET represents a resistance mechanism to epidermal growth factor receptor (EGFR) inhibition in EGFR mutant (mt) non-small cell lung cancer (NSCLC). This Phase 2 study tested whether acquired resistance to erlotinib in MET protein positive NSCLC patients enriched for EGFRmt can be overcome by emibetuzumab plus erlotinib.
Patient and Methods: Patients with Stage IV NSCLC with acquired resistance to erlotinib and MET diagnostic (+) (≥ 10% of cells expressing MET at ≥ 2+ IHC staining intensity at any time) were randomized (3:1) to receive emibetuzumab 750 mg every 2 weeks with or without erlotinib 150 mg once daily. The primary objective was to evaluate the overall response rate (ORR) relative to historic control, with a co-primary objective of ORR in patients with MET expression in ≥ 60% of cells ≥ 2+ (MET ≥ 60%).
Results: One hundred and eleven MET+ patients received emibetuzumab plus erlotinib (N = 83) or emibetuzumab monotherapy (N = 28). 89 of 111 MET+ samples were post-erlotinib. ORR was 3.0% for emibetuzumab plus erlotinib (95% CI: 0.4, 10.5) and 4.3% for emibetuzumab (95% CI: 0.1, 21.9), in patients with post-erlotinib progression biopsies available (n = 89). Similar results were observed in patients with MET ≥ 60% expression (n = 74). Disease control rate and progression-free survival were higher for emibetuzumab plus erlotinib (50%/3.3 months) than for emibetuzumab (26%/1.6 months). No unexpected safety signals emerged. Partial responses were observed in patients with and without EGFRmt or MET amplification. EGFR sensitizing mutations were identified retrospectively in 84.2% of those with available tissue (85/101).
Conclusion: Acquired resistance to erlotinib in MET diagnostic (+) patients was not reversed by emibetuzumab plus erlotinib or emibetuzumab monotherapy, although a subset of patients obtained clinical benefit.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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