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    Home > Active Ingredient News > Antitumor Therapy > One Literature Conference: Eight Popular Targets and Drugs for Lung Cancer (with table attached)

    One Literature Conference: Eight Popular Targets and Drugs for Lung Cancer (with table attached)

    • Last Update: 2021-07-30
    • Source: Internet
    • Author: User
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    Non-small cell lung cancer accounts for about 80% of all lung cancers and can be said to be the most common and important type of lung cancer
    .
    Its treatment methods mainly include surgery, radiotherapy, chemotherapy,
    immunization and targeting
    .
    However, since most patients are in the middle or late stage when they are discovered, it is difficult to cure and the survival rate is low

    .
    At this time, if the mutant gene is found and targeted drugs are given, the survival rate can be greatly improved

    .

    Non-small cell lung cancer accounts for about 80% of all lung cancers and can be said to be the most common and important type of lung cancer
    .
    Its treatment methods mainly include surgery, radiotherapy, chemotherapy,
    immunization and targeting
    .
    However, since most patients are in the middle or late stage when they are discovered, it is difficult to cure and the survival rate is low

    .
    At this time, if the mutant gene is found and targeted drugs are given, the survival rate can be greatly improved

    .
    immunity

    There are many gene mutations in lung cancer patients, and most of the gene mutations (about 40%) are still unknown
    .
    Although the most frequently occurring KRAS mutations account for 25-30% of adenocarcinomas, the first targeted drug sotorasib did not appear until May this year

    .
    Other well-known and important targets include EGFR, ALK, and ROS1

    .
    In addition, there are BRAF V600E mutation, NTRK 1/2/3 gene fusion, MET 14 exon jumping mutation, RET rearrangement and so on

    .

    There are many gene mutations in lung cancer patients, and most of the gene mutations (about 40%) are still unknown
    .
    Although the most frequently occurring KRAS mutations account for 25-30% of adenocarcinomas, the first targeted drug sotorasib did not appear until May this year

    .
    Other well-known and important targets include EGFR, ALK, and ROS1

    .
    In addition, there are BRAF V600E mutation, NTRK 1/2/3 gene fusion, MET 14 exon jumping mutation, RET rearrangement and so on

    .

     

     

    Data source: NCCN NSCLC

    Data source: NCCN NSCLC NSCLC

     

     

    EGFR inhibitor

    EGFR inhibitor EGFR inhibitor

    1st generation: Erlotinib*, Gefitinib*

    1st generation: Erlotinib*, Gefitinib*

    2nd generation: afatinib*, dacomitinib*

    2nd generation: afatinib*, dacomitinib*

    3rd generation: osimertinib*

    3rd generation: osimertinib*

    (* Listed in China)

    (* Listed in China)

    EGFR gene mutation is the most common target in non-small cell lung cancer, accounting for 15-20% of adenocarcinomas
    .
    The proportion is even higher in Asian races, reaching up to 62% in some Asian regions

    .
    In addition, EGFR mutations often occur in non-smokers/previously light smokers

    .

    EGFR gene mutation is the most common target in non-small cell lung cancer, accounting for 15-20% of adenocarcinomas
    .
    The proportion is even higher in Asian races, reaching up to 62% in some Asian regions

    .
    In addition, EGFR mutations often occur in non-smokers/previously light smokers

    .

    The most common mutations in the EGFR gene include: deletion of exon 19 and L858R mutation of exon 21.
    The treatments are as follows:
     

    The most common mutations in the EGFR gene include: deletion of exon 19 and L858R mutation of exon 21.
    The treatments are as follows:
     

    First-line recommendation: 

    First-line recommendation: First-line recommendation: 

    Osimertinib is the first choice because it does not induce T790M resistance and inhibits tumor cell growth for the longest time
    .
    Erlotinib can also be used in combination with VEGF antibodies: Erlotinib + ramucirumab (NCCN recommended level 2A); Erlotinib + bevacizumab, only for non-squamous cell carcinoma (NCCN recommended Level 2B)

    .

    Osimertinib is the first choice because it does not induce T790M resistance and inhibits tumor cell growth for the longest time
    .
    Erlotinib can also be used in combination with VEGF antibodies: Erlotinib + ramucirumab (NCCN recommended level 2A); Erlotinib + bevacizumab, only for non-squamous cell carcinoma (NCCN recommended Level 2B)

    .

    Resistance to the first and second generation EGFR inhibitors: 

    Resistance to EGFR inhibitors of the first and second generations : Resistance to EGFR inhibitors of the first and second generations: 

    60% of patients who use the first and second generations of EGFR inhibitors will develop resistance.
    The mechanisms include two types: T790M mutation and histological changes in non-small cell lung cancer into small cell lung cancer

    .
    Therefore, when the tumor progresses after the first and second-generation EGFR inhibitors are used in patients, genetic testing should be performed to check whether T790M is mutated

    .

    60% of patients who use the first and second generations of EGFR inhibitors will develop resistance.
    The mechanisms include two types: T790M mutation and histological changes in non-small cell lung cancer into small cell lung cancer

    .
    Therefore, when the tumor progresses after the first and second-generation EGFR inhibitors are used in patients, genetic testing should be performed to check whether T790M is mutated

    .

    If the T790M mutation is positive, change the third-generation EGFR inhibitor osimertinib; 

    If the T790M mutation is positive, change the third-generation EGFR inhibitor osimertinib; 

    If other mutant gene targets are found during genetic testing, use corresponding targeted inhibitors; 

    If other mutant gene targets are found during genetic testing, use corresponding targeted inhibitors; 

    If there is no mutated gene target, switch to a platinum-based chemotherapy regimen, which is the same as the chemotherapy regimen for non-small cell lung cancer without EGFR mutations;

    If there is no mutated gene target, switch to a platinum-based chemotherapy regimen, which is the same as the chemotherapy regimen for non-small cell lung cancer without EGFR mutations;

     There is currently no evidence that immunotherapy is effective for patients with EGFR mutations
    .

     There is currently no evidence that immunotherapy is effective for patients with EGFR mutations
    .

    Resistance to third-generation EGFR inhibitors:

    Resistance to third-generation EGFR inhibitors: Resistance to third-generation EGFR inhibitors:

    There are currently no new targeted drugs for resistance to third-generation EGFR inhibitors
    .
    Genetic testing can be performed again to try to find out if there are other mutant gene targets, and if so, use the corresponding targeted inhibitors;

    There are currently no new targeted drugs for resistance to third-generation EGFR inhibitors
    .
    Genetic testing can be performed again to try to find out if there are other mutant gene targets, and if so, use the corresponding targeted inhibitors;

    If there are no other mutant gene targets, switch to a platinum-based chemotherapy regimen, which is the same as the chemotherapy regimen for non-small cell lung cancer without EGFR mutations; 

    If there are no other mutant gene targets, switch to a platinum-based chemotherapy regimen, which is the same as the chemotherapy regimen for non-small cell lung cancer without EGFR mutations; 

    For immunotherapy, there is currently a trial (Inpower150) that proves that on the basis of a two-drug chemotherapy regimen based on bevacizumab + platinum, plus PD-L1 atilizumab can increase the progression-free survival time and survival period
    .
    However, other experiments (Impower130) gave different conclusions

    .

    For immunotherapy, there is currently a trial (Inpower150) that proves that on the basis of a two-drug chemotherapy regimen based on bevacizumab + platinum, plus PD-L1 atilizumab can increase the progression-free survival time and survival period
    .
    However, other experiments (Impower130) gave different conclusions

    .

    Other treatments:

    Other treatments: Other treatments:

    In addition, there are some uncommon mutations in the EGFR gene, such as EGFR S768I, L861Q and G719X mutations.
    Afatinib is recommended

    .
    Of course, afatinib can also be used for the common deletion of exon 19 and L858R mutation of exon 21

    .
    When afatinib cannot be used, osimertinib can be considered

    .

    In addition, there are some uncommon mutations in the EGFR gene, such as EGFR S768I, L861Q and G719X mutations.
    Afatinib is recommended

    .
    Of course, afatinib can also be used for the common deletion of exon 19 and L858R mutation of exon 21

    .
    When afatinib cannot be used, osimertinib can be considered

    .

    The latest international developments:

    International latest developments: International latest developments:

    For lung cancer patients with EGFR 20 exon insertion mutations and progress after chemotherapy, Amivantamab is recommended (this drug was approved by the FDA in May this year and is a dual-target EGFR/MET drug)
    .

    For lung cancer patients with EGFR 20 exon insertion mutations and progress after chemotherapy, Amivantamab is recommended (this drug was approved by the FDA in May this year and is a dual-target EGFR/MET drug)
    .
    FDA

     

    ALK inhibitor

    ALK inhibitorALK inhibitor

    1st generation: Crizotinib*

    1st generation: Crizotinib*

    2nd generation: Ceritinib*, aletinib*, brigatinib

    2nd generation: Ceritinib*, aletinib*, brigatinib

    3rd generation: Loratinib

    3rd generation: Loratinib

    (* Listed in China)

    (* Listed in China)

    The second most common target is the ALK gene mutation, which accounts for 7% of adenocarcinomas.
    It is often found in patients who do not smoke or have a history of mild smoking

    .

    The second most common target is the ALK gene mutation, which accounts for 7% of adenocarcinomas.
    It is often found in patients who do not smoke or have a history of mild smoking

    .

    First-line recommendation:

    First-line recommendation: First-line recommendation:

    NCCN recommends second-generation ALK inhibitors as the first-line treatment, with aletinib being the first choice.
    This choice is based on the results of long-term observations in clinical trials;

    NCCN recommends second-generation ALK inhibitors as the first-line treatment, with aletinib being the first choice.
    This choice is based on the results of long-term observations in clinical trials;

    As there is no clinical trial for direct comparison between second-generation drugs, brigatinib can also be used as a first-line treatment
    .

    As there is no clinical trial for direct comparison between second-generation drugs, brigatinib can also be used as a first-line treatment
    .

    Laura imatinib may be selected as one of the first-line treatment, but because of its prominent adverse reactions (neurocognitive and mood changes, liver high cholesterol hyperlipidemia), and because of its clinical trials of observation time is short, for Laura Nitra is not the first choice medicine
    .

    Laura imatinib may be selected as one of the first-line treatment, but because of its prominent adverse reactions (neurocognitive and mood changes, liver high cholesterol hyperlipidemia), and because of its clinical trials of observation time is short, for Laura Nitra is not the drug of choice
    .
    cholesterol

    Emergence of resistance 

    Emergence of drug resistance 

    If resistance to ALK inhibitors appears, the "upgrading" approach can be adopted
    .
    That is: for the first generation of ALK inhibitor crizotinib drug resistance, you can use the second generation of ALK inhibitors ceritinib, aletinib, brigatinib

    .
    If there is drug resistance to the second-generation ALK inhibitor, the third-generation ALK inhibitor loratinib can be used

    .

    If resistance to ALK inhibitors appears, the "upgrading" approach can be adopted
    .
    That is: for the first generation of ALK inhibitor crizotinib drug resistance, you can use the second generation of ALK inhibitors ceritinib, aletinib, brigatinib

    .
    If there is drug resistance to the second-generation ALK inhibitor, the third-generation ALK inhibitor loratinib can be used

    .

    Other treatments:

    Other treatments: Other treatments:

    Patients with ALK gene mutations can basically be sure that there are no EGFR gene mutations, so EGFR inhibitors are ineffective; there is currently no evidence that immunotherapy is effective for patients with ALK mutations
    .

    Patients with ALK gene mutations can basically be sure that there are no EGFR gene mutations, so EGFR inhibitors are ineffective; there is currently no evidence that immunotherapy is effective for patients with ALK mutations
    .

      

      

    ROS1

    ROS1 ROS1

    Crizotinib* Ceritinib*

    Crizotinib* Ceritinib*

    Lauratinib Entratinib

    Lauratinib Entratinib

    (* Listed in China)

    (* Listed in China)

    The probability of ROS1 mutation in non-small cell lung cancer is about 1-2%, and it is often found in adenocarcinoma, young patients, non-smokers, or patients with a history of mild smoking
    .

    The probability of ROS1 mutation in non-small cell lung cancer is about 1-2%, and it is often found in adenocarcinoma, young patients, non-smokers, or patients with a history of mild smoking
    .

    First-line recommendation: 

    First-line recommendation: First-line recommendation: 

    For patients with ROS1 mutations, the FDA recommends Crizotinib (ROS1/MET inhibitor) and Entratinib (ROS1/TRK inhibitor) as the first choice
    .
     

    For patients with ROS1 mutations, the FDA recommends Crizotinib (ROS1/MET inhibitor) and Entratinib (ROS1/TRK inhibitor) as the first choice
    .
     

    Crizotinib resistance:

    Crizotinib resistance: Crizotinib resistance:

    Loratinib is recommended as an option after crizotinib resistance
    .

    Loratinib is recommended as an option after crizotinib resistance
    .

    Other treatments: 

    Other treatments: Other treatments: 

    Immunotherapy is effective, with an objective response rate of 17%
    .

    Immunotherapy is effective, with an objective response rate of 17%
    .

     

     

    KRAS G12C

    KRAS G12C KRAS G12C

    Sotorasib

    Sotorasib

    latest progress:

    Latest development: Latest development:

    In May 2021, Sotorasib was approved by the FDA as the first targeted drug for non-small cell lung cancer with KRAS G12C mutation and at least one systemic treatment in the past
    .
     

    In May 2021, Sotorasib was approved by the FDA as the first targeted drug for non-small cell lung cancer with KRAS G12C mutation and at least one systemic treatment in the past
    .
     

    In an early one-arm trial, 59 patients with KRAS G12C mutation who had previously used at least one systemic treatment for non-small cell lung cancer had a remission rate of 32% after treatment with sotorasib, with a median PSF of 6.
    3 months

    .
    Adverse reactions ≥ grade 3 include abnormal liver function tests and diarrhea

    .
    At the same time, sotorasib cannot be used together with PPI, H2 receptor antagonist, strong CYP3A4 inducer, part of CYP3A4 substrate, and part of P-gp substrate due to drug interaction

    .

    In an early one-arm trial, 59 patients with KRAS G12C mutation who had previously used at least one systemic treatment for non-small cell lung cancer had a remission rate of 32% after treatment with sotorasib, with a median PSF of 6.
    3 months

    .
    Adverse reactions ≥ grade 3 include abnormal liver function tests and diarrhea

    .
    At the same time, sotorasib cannot be used together with PPI, H2 receptor antagonist, strong CYP3A4 inducer, part of CYP3A4 substrate, and part of P-gp substrate due to drug interaction

    .

     

    Other mutant genes

    Other mutant genes Other mutant genes

    BRAF V600E, NTRK 1/2/3 gene fusion, MET 14 exon jumping mutation, RET rearrangement

    BRAF V600E, NTRK 1/2/3 gene fusion, MET 14 exon jumping mutation, RET rearrangement

    In addition to these common mutations, mutations in patients with NSCLC as well BRAF V600E, NTRK 1/2/3 fusion gene, MET 14 mutation in exon skipping, RET rearrangements and the like
    .
    The incidence is not high, and there are not many choices of drugs

    .
    See the summary table for related treatment methods .

    In addition to these common mutations, mutations in patients with NSCLC as well BRAF V600E, NTRK 1/2/3 fusion gene, MET 14 mutation in exon skipping, RET rearrangements and the like
    .
    The incidence is not high, and there are not many choices of drugs

    .
    See the summary table for related treatment methods .

     

     

    Finally, for your convenience, the summary table is hereby released as follows:

    Finally, for your convenience, the summary table is hereby released as follows:

    Reference materials:

    References: 1.
    NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer (Version 2.
    2021)
    2.
    UpToDate: Rogerio C Lilenbaum.
    Systemic therapy for advanced non-small cell lung cancer with an activating mutation in the epidermal growth factor receptor .
    last updated: Jun 02, 2021.
    Available at: https:// in-the-epidermal-growth-factor-receptor?search=EGFR&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4#H1
    3.
    UpToDate: Lecia V Sequist, Joel W Neal.
    Personalized, genotype-directed therapy for advanced non-small cell lung cancer.
    last updated: Jul 09, 2021.
    Available at: https:// personalized-genotype-directed-therapy-for-advanced-non-small-cell-lung-cancer?search=target%20lung%20cancer&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H3902134
    4.
    UpToDate: Benjamin Solomon, Christine M Lovly.
    Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer.
    last updated: May 07, 2021.
    Available at:https:// -oncogene-positive-non-small-cell-lung-cancer?search=target%20lung%20cancer&topicRef=16538&source=see_link
    5.
    Socinski MA, Jotte RM, Cappuzzo F, et al.
    Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC.
    N Engl J Med.
    2018;378(24):2288-2301.
    doi:10.
    1056/NEJMoa1716948
    6.
    West H , McCleod M, Hussein M, et al.
    Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, .
    open-label, phase 3 trial Lancet Oncol 2019; 20 (7):.
    .
    924-937 doi: 10.
    1016 / S1470-2045 (19) 30167-6


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