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    Home > Active Ingredient News > Antitumor Therapy > Professor Zheng Xiangqian: From global data to Chinese data, platinib continues to illuminate the treatment of patients with RET variant advanced thyroid cancer

    Professor Zheng Xiangqian: From global data to Chinese data, platinib continues to illuminate the treatment of patients with RET variant advanced thyroid cancer

    • Last Update: 2021-09-30
    • Source: Internet
    • Author: User
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    Introduction RET is an important driver gene for medullary thyroid carcinoma (MTC) and differentiated thyroid cancer (DTC).
    Studies have shown that more than 95% of hereditary MTC and about 50% of sporadic MTC patients have RET mutations, while 10%~ 20% of patients with papillary thyroid cancer are RET fusion positive 1-2
    .

    At the forthcoming American Thyroid Association (ATA) annual meeting, the RET inhibitor pratinib in the treatment of RET variant solid tumors ARROW study Chinese advanced MTC patients cohort results in "Late-breaking Abstract" (LBA, Late-breaking Abstract) Form was selected for this year's ATA conference, injecting new vitality into China's MTC diagnosis and treatment pattern
    .

    Yimaitong specially invited Professor Zheng Xiangqian from Tianjin Medical University Cancer Hospital to share research results and analyze the pain points of current diagnosis and treatment
    .

    Professor Zheng Xiangqian, Director of the Department of Thyroid and Neck Oncology, Tianjin Medical University Cancer Hospital, Doctoral Supervisor, Member of the Standing Committee and Secretary-General of the Thyroid Cancer Professional Committee of the Chinese Anti-Cancer Association Member and Secretary-General of the Head and Neck Tumor Professional Committee of the Chinese Anti-Cancer Association Executive Director, Chinese Medical Association Oncology Branch Youth Committee Executive Director, China Medical Education Association Deputy Chairman, Head and Neck Tumor Professional Committee, China Medical Education Association, Member of the Asia-Pacific Thyroid Association (AOTA) Targeted therapy has become radioactive iodine resistant or unresectable thyroid cancer patients An important treatment method, which can reduce the symptoms of patients and prolong the survival time of patients
    .

    At present, the drugs approved for the treatment of MTC in China are all multi-target kinase inhibitors (MKI), which bring curative effects.
    At the same time, "off-target" effects lead to a higher incidence of adverse reactions, which may easily cause drug interruption or discontinuation, which will affect Therapeutic effect
    .

    MKI drugs are prone to RET V804L/M gatekeeper mutations leading to drug resistance3
    .

    Therefore, clinical treatment of thyroid cancer urgently needs a drug that specifically targets the RET target
    .

    Pratinib (BLU-667) is an oral tyrosine kinase inhibitor that can efficiently and selectively target oncogenic RET fusions and mutations (including the V804 guard mutation related to multikinase inhibitor resistance), and exerts anti- Tumor effect 4-5
    .

    Professor Zheng Xiangqian said that in June of this year, the global population results of pratinib in the treatment of advanced RET variant thyroid cancer have been published in the journal Lancet Diabetes Endocrinol
    .

    The results of the ARROW study of the Chinese advanced MTC patient cohort were selected as the LBA of the ATA Annual Meeting, which once again reflects the important clinical value of the study, and provides an important reference for exploring innovative treatment methods suitable for Chinese patients
    .

    ARROW study design The ARROW study of pratinib in the treatment of RET variant solid tumors is a global multi-center, multi-cohort, open-label phase I/II clinical study, which includes the first phase of dose escalation and the second phase of dose expansion Part
    .

    According to the patient's disease type and previous treatment status, the second phase of the study included patients with unresectable RET variant locally advanced and metastatic solid tumors aged ≥18 years
    .

    The RET mutation is confirmed by tumor tissue or blood DNA/RNA detection
    .

    Patients in the second phase of the study received pratinib 400 mg, QD treatment until the disease progressed, intolerance, informed consent was withdrawn, or the investigator terminated the treatment
    .

    The primary endpoint of the second phase is ORR
    .

    Secondary endpoints include duration of remission (DOR), clinical benefit rate [defined as complete remission (CR), partial remission (PR) or stable disease (SD) ≥ 16 weeks], disease control rate (DCR, CR, PR, SD rate), progression-free survival (PFS) and overall survival (OS)
    .

    Specific endpoints of MTC include the biochemical response rate of serum calcitonin and carcinoembryonic antigen levels
    .

    The included RET-mutant MTC patients in the global population included naïve and treated patients, and patients with RET fusion-positive thyroid cancer were treated patients after standard treatment
    .

    The Chinese MTC cohort consists of patients without previous systemic treatment (except chemotherapy)
    .

    CT/MRI evaluates the curative effect every 8 weeks
    .

    Follow-up monitoring of MTC patients' serum calcitonin, carcinoembryonic antigen levels and disease-related diarrhea
    .

    Pratinib is effective in the treatment of RET-mutated thyroid cancer, bringing life to patients with RET-mutated thyroid cancer.
    Global cohort data: The latest global population data show that pratinib treats advanced-stage RET-mutated MTC, cabozantinib and cabozantinib globally.
    / Or vandetanib has an objective response rate (ORR) of 71%, 60%, and 89% in patients with RET-mutant MTC and RET-fusion-positive thyroid cancer, respectively3
    .

    China cohort data: The report of this conference shows that as of April 12, 2021, the Chinese MTC patient cohort included 34 patients with advanced MTC, of ​​which 28 patients tested positive for RET mutations, and 96.
    4% (27/28) of the patients were at baseline It is the IVC period
    .

    Except for one patient, none of the other patients received systemic treatment
    .

    The patient takes 400 mg of pratinib orally every day
    .

    Research data 6 showed that among 26 patients with measurable lesions reviewed by a blind independent center, the objective response rate (ORR) was 73.
    1% (95% CI; 52.
    2, 88.
    4), of which 3 cases (11.
    5%) ) The patient has achieved complete remission (CR)
    .

    The disease control rate (DCR) was 84.
    6% (95% CI; 65.
    1, 95.
    6)
    .

    The median duration of remission was 5.
    75 months (1.
    8-12.
    8), the median duration of remission (DOR) had not yet been reached, the 6-month DOR rate and the 9-month DOR rate were both 100%6
    .

    Studies have confirmed that pratinib has sustained anti-tumor activity in the treatment of RET mutation-positive Chinese MTC patients, and has shown an efficacy consistent with the global patient population
    .

    As of July 11, 2019 (the cut-off time for the efficacy evaluation), the efficacy results of each group are as follows: Table 1 Tumor remission status of the Chinese population and the global population Figure 1.
    DOR and none of RET mutant MTC and RET fusion-positive thyroid cancer patients in the global population Progressive survival (PFS) Pratinib is well tolerated in patients with RET-mutated advanced thyroid cancer.
    Global cohort data: Pratinib in patients with RET-mutated thyroid cancer has common treatment-related adverse events of grade ≥3 (≥10%) Hypertension (17%, 24/142), neutropenia (14%, 19 cases), lymphopenia (12%, 17 cases) and anemia (10%, 14 cases)
    .

    In addition, 21 patients (15%) had serious treatment-related adverse events, of which the most common (>2%) was pneumonia (4%, 5 cases)
    .

    There were no new adverse reactions in the Chinese population, and no patients stopped treatment or died due to treatment-related adverse events (TRAEs)
    .

    Professor Zheng Xiangqian said that whether it is the global patient population data of the ARROW study or the Chinese patient population data, pratinib has shown good efficacy and manageable tolerability in RET mutation-positive advanced MTC and RET fusion-positive thyroid cancer.
    , Improve the patient's survival benefit
    .

    In addition, the once-daily oral medication greatly improves patient compliance and convenience
    .

    At present, pratinib has been approved in the United States for the treatment of advanced or metastatic RET-mutated MTC patients aged 12 years and older who require systemic therapy and patients with advanced or metastatic RET fusion-positive thyroid cancer that require systemic therapy and are refractory to radioactive iodine.

    .

    Pratinib capsule) has been accepted by the National Medical Products Administration (NMPA) and has been included in the priority review.
    The extended indications include late or metastatic RET genes that require systemic treatment for 12 years and older.
    Mutant MTC, and advanced or metastatic RET fusion-positive thyroid cancer that requires systemic treatment and is refractory to radioactive iodine (if radioactive iodine is suitable) for 12 years and older
    .

    The 2021 edition of CSCO "Differentiated Thyroid Cancer Guidelines" included RET fusion gene detection into the pathological diagnosis recommendation for the first time (level II recommendation).
    At the same time, pratinib was included for the first time in the RET fusion gene-positive DTC molecular targeted drug recommendation (II) Level recommendation)
    .

    It is expected that in the near future, platinib will be approved for marketing in China, promoting and changing the current status of targeted therapy for RET mutation-positive advanced MTC and RET fusion-positive thyroid cancer in China, and bringing new strategies and new methods to patients who are in urgent need of clinical treatment.
    The dawn of hope
    .

    References 1.
    Kato S, Subbiah V, Marchlik E, Elkin SK, Carter JL, Kurzrock R.
    RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients.
    Clin Cancer Res.
    2017;23(8):1988-1997.
    2 , Subbiah V, Gainor JF, Rahal R, et al.
    Precision Targeted Therapy with BLU-667 for RET-Driven Cancers.
    Cancer Discov.
    2018;8(7):836-849.
    3, Subbiah V, Hu MI, Wirth LJ, et al.
    Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study.
    Lancet Diabetes Endocrinol.
    2021;9(8):491-501.
    4, Carlomagno F, Guida T, Anaganti S, et al.
    Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors.
    Oncogene.
    2004;23(36):6056-6063.
    5, Bentzien F, Zuzow M, Heald N, et al.
    In vitro and in vivo activity of cabozantinib (XL184),an inhibitor of RET, MET, and VEGFR2, in a model of medullary thyroid cancer.
    Thyroid.
    2013;23(12):1569-1577.
    6, 90th Annual Meeting of the American Thyroid Association (oxfordabstracts.
    com)https://virtual.
    oxfordabstracts.
    com/#/event/2083/submission/446 Material number: NPM-CN-TC-003-20210923
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