Author of

• 18502

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  P3.02c - Poster Session with Presenters Present (ID 472)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18508

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    P3.02c-006 - EGFR and HER3 Inhibition - A Novel Therapy for Invasive Mucinous Non-Small Cell Lung Cancer Harboring an NRG1 Fusion Gene (ID 4272)

    14:30 - 14:30  |  Author(s): M. Hasman
    • Abstract

    Background:
    Invasive mucinous adenocarcinoma of the lung (IMA) accounts for 2 to 10% of all lung adenocarcinomas and usually presents as a multifocal and unresectable disease for which no effective treatment exists. Recently, rearrangements of the HER3 ligand gene NRG1 have been identified in IMA such as NRG1-SLC3A2 and NRG1-CD74 leading to activation of HER3 and PI3K-AKT signaling pathways. Therefore, IMA harboring NRG1 fusion genes may serve as a biologically attractive target for HER3-targeted therapies.
    
    Methods:
    Study NCT01482377 is a phase Ib study analyzing the safety and preliminary efficacy of lumretuzumab, a monoclonal anti-HER3 antibody, in combination with erlotinib in patients with HER3 protein-positive tumors. Lumretuzumab IV was given every 2 weeks at 800 mg and erlotinib was given at standard dose of 150 mg/d po. A pretreatment tumor biopsy was mandated for the assessment of membranous HER3 protein by IHC. NRG1 fusion genes were identified by RT-PCR and sequencing. Tumor assessments were performed by CT scans every 8 weeks. Therapy was given until progressive disease or unacceptable toxicity. Here we describe the clinical course of two patients with IMA harboring a SLC3A2-NRG1 fusion gene treated within this study.
    
    Results:
    Patient 1 is a 55-year-old Asian female who was diagnosed in 2011. Previous lines of therapy included gemcitabine and cisplatin, erlotinib, pemetrexed, docetaxel and irinotecan and cisplatin. After enrolling into the study the first CT scan showed a decrease of 16% of the target lesion qualifying for stable disease per RECIST 1.1. At the following tumor assessment progressive disease was documented resulting in a disease stabilization of 16.4 weeks. Patient 2 is a 42-year-old Asian female who was diagnosed in 2013. Previous lines of therapy included pemetrexed and cisplatin, erlotinib, docetaxel, vinorelbine, and gemcitabine and cisplatin. After enrolling into the study, the patient showed stable disease as a best overall RECIST response that lasted 16.3 weeks. Both patients experienced mild to moderate rash and diarrhea (grade 1 & 2). No ≥ grade 3 adverse events were observed.
    
    Conclusion:
    This is the first report of a novel targeted therapy approach in IMA patients harboring NRG1 gene rearrangements - a histological entity that is generally considered to be extremely difficult to treat. The combination of lumretuzumab and erlotinib was well tolerated and showed signs of tumor shrinkage in a heavily pretreated IMA patient. Further studies are warranted to elucidate the clinical relevance of HER3-targeted therapy in IMA patients with NRG1 fusion genes.