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    Home > Active Ingredient News > Antitumor Therapy > Can targeted drugs be tested blindly?

    Can targeted drugs be tested blindly?

    • Last Update: 2021-11-14
    • Source: Internet
    • Author: User
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    Nearly half of patients with non-small cell lung adenocarcinoma can detect EGFR gene mutations, 90% of which are deletion mutations in exon 19 (19del) and missense mutations in exon 21 (21L858R)
    .

    Among the remaining mutation sites, insertion mutations in exon 20 accounted for 4-12% of EGFR mutations, and belonged to the third most common mutation in the EGFR gene
    .

    There are many types of insertion mutations in exon 20 of the EGFR gene.
    There are many types of insertion mutations in exon 20.
    At present, more than 60 types of insertion mutations have been reported, and these types have different responses to different targeted drugs
    .

    It has been reported that the A763_Y764insFQEA of the EGFR gene has abnormal sensitivity to the first and second generation EGFR targeted drugs
    .

    In the LUX-LUNG clinical trial, the second-generation EGFR-targeting drug afatinib has limited efficacy in non-small cell lung cancer patients with EGFR gene exon 20 insertion mutations (ex20ins), and progression-free survival (PFS) It was 2.
    7 months, and the overall survival (OS) was 9.
    2 months
    .

    For the third-generation EGFR targeted drugs, osimertinib, ametinib and vomitinib are currently of more concern
    .

    There are reports showing that osimertinib is effective against insertion mutations in exon 20 of the EGFR gene; there are also studies claiming that different mutation sites may have different therapeutic effects
    .

    There are also studies that give pessimistic data: 21 patients used 80 mg of osimertinib daily, the treatment response rate was only 5%, the median progression-free survival time was 3.
    6 months, and the median overall survival time was only 8.
    7 Months
    .

    There are different opinions and the conclusions are controversial, so many patients choose to blindly test the third-generation EGFR-targeted drugs
    .

    The risk of blind testing is that once the efficacy is poor, drug resistance will soon develop.
    Not only is there no follow-up drug available, but because the patient's first-line treatment is already drug-resistant, they often lose the opportunity to participate in clinical trial treatment
    .

    Because many targeted drug clinical trials require untreated patients, this directly leads to passive follow-up treatment
    .

    So, does the third-generation targeted drug osimertinib have any effect on the insertion mutation of exon 20 of the EGFR gene? The following research answers this question
    .

    Osimertinib has limited efficacy against insertion mutations in exon 20 of the EGFR gene.
    This is a prospective, single-arm, multi-center clinical trial that started in August 2018 and included a total of 14 EGFRs by January 2020.
    Patients with mutations in exon 20 of the gene
    .

    The actual number of patients taking the drug is 12, and the patient's dose of osimertinib is 80 mg per day
    .

    Figure 1.
    EGFR gene exon 20 insertion mutation using osimertinib efficacy data.
    Among the 12 patients undergoing efficacy evaluation, none of the patients could be evaluated as responding to osimertinib treatment, and 7 patients were in stable condition ( (Accounting for about 58.
    3%); 5 patients have progressed (accounting for 41.
    7%)
    .

    The median progression-free survival time for all patients was 3.
    8 months, and the median overall survival time was 15.
    8 months
    .

    Compared with the performance of osimertinib in 19del or 21L858R point mutation, this data can be said to be dismal
    .

    The researchers continued to analyze the types of gene mutations in these patients and the inhibitory activity of osimertinib in vitro at these different mutation sites
    .

    That is, if the in vitro test finds that the drug concentration of osimertinib inhibits a certain mutation is high, the use of osimertinib is often ineffective for that type of patient
    .

    Figure 2.
    Types of mutations in exon 20 of the EGFR gene and the inhibitory activity of osimertinib are shown in the figure above.
    For the mutation types marked in red boxes, if this type of gene mutation is inhibited, a high concentration of osimertinib is required.
    It is impossible to achieve in oral administration of osimertinib.
    Therefore, the treatment effect of osimertinib in such patients is very poor, and they often become resistant within one month
    .

    For these patients, the most important opportunity is to participate in clinical trials specifically targeting the insertion mutation in exon 20 of the EGFR gene, rather than blindly testing osimertinib or other third-generation targeted drugs
    .

    Implications: Carefully choose treatment measures.
    In many patient communities, when the counselor gives his own genetic test report, if it is an insertion mutation in exon 20 of the EGFR gene, many patients will recommend the use of third-generation targeted drugs
    .

    Indeed, there are some research reports or data that give success stories
    .

    However, through today’s cancer degree sharing, I hope everyone can understand the possible risks
    .

    The mutation in exon 20 of the EGFR gene contains nearly 60 different mutation types, and different mutation types determine the use of different drugs and treatment measures
    .

    If the EGFR gene 20 insertion mutation is found using traditional gene sequencing, it is strongly recommended to use the second-generation gene sequencing technology to test it again, at least to determine the location of the mutation
    .

    In the gene detection module of the cancer degree app, there are more cost-effective gene detection products, and you can click to select
    .

    Cancer degree reminds everyone that you must carefully analyze your genetic test report information.
    If it is an insertion mutation of exon 20 of the EGFR gene mutation, do not rush to use targeted drugs.
    It depends on the specific mutation site and the guidance for the interpretation of the report.

    .

    If the medicine is not right, it is not only a waste of money, but more importantly, it delays the best treatment opportunity and loses the opportunity to participate in clinical trials
    .

    Tumor treatment is a process of continuous selection.
    We must learn as much as possible about the professional knowledge related to the disease in order to make more favorable choices when needed
    .

    In the Cancer Degree app and the "Global Clinical Trials" WeChat Mini Program, there are many clinical trials solicitation, and patients can follow and apply to participate in the corresponding clinical trials
    .

    However, clinical trials generally require untreated patients.
    If a targeted drug is blindly tested, the effect is only one month, but it is a pity that the opportunity to benefit from clinical trials is lost
    .

    For more anti-cancer knowledge, welcome to search and download the cancer degree app to communicate with similar patients
    .

    Reference: H.
    Yasuda, et al.
    , A phase I/II study of osimertinib in EGFR exon 20 insertion mutation-positive non-small cell lung cancer, Lung Cancer (2021).
    Click below to learn more about clinical trial items Swipe left and right to see more
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