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    Home > Active Ingredient News > Digestive System Information > After being included in the fourth-line level I recommendation of "CSCO Gastrointestinal Stromal Tumor Diagnosis and Treatment Guidelines", ripretinib will soon be approved for marketing in China

    After being included in the fourth-line level I recommendation of "CSCO Gastrointestinal Stromal Tumor Diagnosis and Treatment Guidelines", ripretinib will soon be approved for marketing in China

    • Last Update: 2021-04-21
    • Source: Internet
    • Author: User
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    On March 19, 2021, the official website of the National Medical Products Administration (NMPA) showed that the application for marketing of ripretinib is "under review" and it is expected to be approved by the NMPA in the near future for the treatment of patients who have received imatinib including imatinib.
    Adult patients with advanced gastrointestinal stromal tumor (GIST) treated with 3 or more kinase inhibitors.

    Author: cornflower This article is the author's permission NMT Medical publish, please do not reprint without authorization.

    GIST is the most common gastrointestinal interstitial tumor.
    In recent years, with the improvement of diagnosis and treatment technology, its incidence has been increasing year by year.

    Although it is a rare disease, there is a huge patient population in our country, and the annual number of patients has exceeded tens of thousands.

    GIST's first, second, and third-line treatment drugs are imatinib approved in 2002, sunitinib approved in 2006, and regorafenib approved in 2013.

    However, studies have found that advanced GIST, especially advanced GIST that has progressed after receiving TKI treatment, is often accompanied by multiple secondary mutations.

    However, clinically, it is difficult to obtain tissue samples, and the opportunity to identify secondary mutations may be missed.

    Therefore, the posterior treatment of GIST requires not only strong effects, but also a broad spectrum of therapeutic drugs to save the lives of patients.

    The emergence of Ripretinib meets this urgent clinical need.

    In 2020, my country’s first edition of "Guidelines for Diagnosis and Treatment of Gastrointestinal Stromal Tumors" was released.
    Ripertinib is recommended for metastatic GIST after failure of third-line treatment, and it is the first-level recommendation of type I evidence [1], and it is the only one in the guideline.
    The fourth-line treatment plan recommended by Level I has become a potential fourth-line standard treatment plan, filling the gap in the fourth-line standard treatment of advanced GIST in my country.

    As shown in the figure, from the perspective of the strength of recommendation, Level I recommendation represents "universal diagnosis and treatment measures with good accessibility (including clear indications), and the value of tumor treatment is relatively stable, which is basically included by the National Medical Insurance.
    "
    The determination of level I recommendation does not change due to commercial medical insurance.
    The main consideration is the clear benefit of patients.

    The unique mechanism of action helps ripretinib overcome drug resistance.
    Ripretinib is a tyrosine kinase switch control inhibitor that regulates the kinase switch and activation loop through a unique dual mechanism of action, thereby extensively inhibiting KIT and PDGFRα mutant kinases [2].

    Previously approved imatinib, sunitinib, regorafenib and avapritinib all act by competitively binding to the ATP kinase binding site; in contrast, ripretinib binds to the kinase switch pocket and activates simultaneously through a dual mechanism Ring switch.

    Studies have shown that for patients who have previously received resistance after TKI treatment, no matter what mutations appear, the kinase is activated by structural changes activated by this switch.

    Therefore, ripretinib is a broad-spectrum inhibitor for KIT and PDGFRA mutations.
    For patients who have developed various types of resistance after TKI treatment, ripretinib may be effective in inhibiting them.

    The mechanism of action of Ripretinib, the picture is from the online clinical study-speak with strength The INVICTUS study is a placebo-controlled, double-blind, international multi-center phase III randomized clinical study, which aims to evaluate the use of ripretinib versus placebo in 129 patients with advanced GIST The safety, tolerability and effectiveness of [3], patients have previously received treatments including imatinib, sunitinib and regorafenib.

    The patients were randomly assigned to the ripretinib group (150 mg per day) or the placebo group at 2:1.

    The results of the study showed that the median progression-free survival (PFS) of patients in the ripretinib group was 6.
    3 months, while the placebo group was only 1.
    0 months, reaching the primary endpoint, and the risk of disease progression or death was significantly reduced by 85% (HR =0.
    15, P<0.
    0001).

    At the same time, the study also reached the secondary endpoints of objective response rate (ORR) and overall survival (OS).

    The ORR of the Ripretinib group was 9.
    4%, while that of the placebo group was 0% (P=0.
    0504).

    The median OS of the Ripretinib group and the placebo group were 15.
    1 months and 6.
    6 months, respectively, and the risk of death was reduced by 64% (HR=0.
    36).

    In terms of safety, the most common adverse reactions (≥20%) are hair loss, fatigue, nausea, abdominal pain, constipation, muscle pain, diarrhea, loss of appetite, palm and plantar swelling syndrome, and vomiting.

    8% of patients had adverse reactions leading to permanent discontinuation, 24% of patients discontinued the dose due to adverse reactions, and 7% of patients reduced the dose due to adverse reactions.

    As a new drug, ripretinib has many topics worth exploring in the future.

    For example, patients with front-line treatment are in better physical condition, and whether the use of ripretinib for <4-line treatment can bring greater benefits to patients and so on.

    In short, ripretinib, a new type of TKI drug, has made many patients with advanced GIST see hope of survival, and it is hoped that ripretinib will be marketed in my country as soon as possible to benefit more patients with advanced GIST.

    References: 1.
    2020 "CSCO Gastrointestinal Stromal Tumor Diagnosis and Treatment Guidelines"; 2.
    Janku F, Abdul Razak AR, Chi P, et al.
    Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal StromalTumor: A Phase I Study of Ripretinib .
    J ClinOncol.
    2020 Aug 17:JCO2000522.
    3.
    BlayJY, SerranoC, HeinrichMC, et al.
    Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind,randomised, placebo-controlled, phase 3 trial.
    Lancet Oncol .
    2020Jul;21(7):923-934.

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