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Profiling Differential Responses to Pan-HER Inhibition

    Cancer Discovery
    |April 5, 2017
    PubMed

    Insights

    Neratinib, a pan-HER inhibitor, showed varied effectiveness in solid tumors with HER2/3 mutations. Responses differed by cancer type, with notable activity in breast and biliary tract cancers but not in bladder or colorectal cancers.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Pharmacology

    Background:

    • The SUMMIT trial investigated neratinib's efficacy in solid tumors with HER2/3 alterations.
    • HER2 and HER3 mutations are implicated in various cancer types.
    • Targeting HER family receptors is a key strategy in cancer therapy.

    Purpose of the Study:

    • To evaluate the clinical activity of neratinib in patients with solid tumors harboring HER2 or HER3 mutations.
    • To determine if specific HER2/3 alterations predict response to neratinib.
    • To assess neratinib's efficacy across different tumor types with these mutations.

    Main Methods:

    • Phase II, multicenter, open-label basket trial design.
    • Enrollment of patients with advanced solid tumors and documented HER2 or HER3 mutations.
    • Treatment with single-agent neratinib, with response assessment via RECIST criteria.

    Main Results:

    • Neratinib demonstrated single-agent activity in breast, biliary tract, and cervical cancers harboring HER2/3 mutations.
    • No responses were observed in bladder and colorectal cancers with these mutations.
    • A subset of patients with HER3 mutations showed no response to neratinib, irrespective of tumor type.

    Conclusions:

    • Response to neratinib in HER2/3-mutated solid tumors is highly dependent on the specific mutation and tumor histology.
    • Neratinib exhibits promising activity in certain HER2/3-altered cancers, warranting further investigation.
    • HER3 mutations may not be predictive of response to neratinib in all cancer contexts.

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