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    Home > Active Ingredient News > Antitumor Therapy > Professor Ma Xuezhen: EGFR sensitive mutant advanced non-small cell lung cancer NSCLC full management should pay attention to the "line" sequence and "face" of the union.

    Professor Ma Xuezhen: EGFR sensitive mutant advanced non-small cell lung cancer NSCLC full management should pay attention to the "line" sequence and "face" of the union.

    • Last Update: 2020-07-30
    • Source: Internet
    • Author: User
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    With the continuous development of medical research, lung cancer has long entered the era of precision medicine. !----currently in China, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) has shown the "three generations of the same" event, EGFR sensitive mutation late non-small cell lung cancer (NSCLC) treatment strategy and how to update? The optimization of The Treatment Strategy of NSCLC in the late Stage Of EGFR Sensitive Mutation is deeply analyzed.extension of OS is the most important treatment target of EGFR sensitive mutation late NSCLC treatment in patients with EGFR sensitive mutation late NSCLC, extended total survival (OS) and progression-free survival (PFS) is an important treatment target, of which extension of OS is the most important and should be the first priority.in the patients we treated, many patients receive targeted treatment to reduce the tumor load, to give local treatment, so that patients into a tumor-free state, can survive 5-10 years, or even more, to achieve long-term survival and even cure possibilities.therefore, I personally think that at this time we should probably pay more attention to whether patients can achieve long-term survival or cure, and secondly, to extend the OS of most patients as much as possible.there are differences in the resistance mechanism of eGFR TKI in each generation, and each generation of EGFR TKI is different in the drug resistance mechanism in order to bring better efficacy to patients.the first generation of EGFR TKI first-line treatment drug resistance will often appear earlier eGFR gene No. 20 exon T790M mutation, the incidence rate is 50% to 60%, and T790M mutation-positive patients followed by the application of the third generation of EGFR TFRtreatment opportunities.AURA3 study, the median PFS was able to reach 10.1 months after the second-generation treatment of the third-generation drug ochedinib in patients with A790M mutation-positive patients who failed treatment.the acquired drug resistance mechanism of the second generation of EGFR TKI (afatinib and dacotini) is similar to that of the first generation of drugs.previous studies showed that 48.8% to 73.1% of patients with Afatinib drug resistance had A790M mutations.ARCHER 1017 study, more than 50% of patients developed t790M mutations when dacotinib was resistant., studies have shown that the second generation of EGFR TKI is more homogenous and delays the occurrence of acquired drug resistance than the first generation of EGFR TKI., some retrospective studies have found that afatinib salinoochtini can provide better objective remission (ORR, 82.9% vs 53.9%) and translate into PFS advantage (median PFS: 15.6 vs 8.9 months) than the first generation of EGFR TKI serial ochitini.the drug ochedinib resistance mechanisms of the third generation of the drug is more complex than that of the first and second generation eGFR TKI.studies show that oxidinib's drug resistance mechanisms include: acquired EGFR mutations, such as C797S mutations, acquired amplification, such as MET amplification, EGFR amplification, changes in acquired cell genes, such as the fusion of acquired carcinogenic genes, and changes in tissue types, such as non-small cell conversion to lung cancer, small cell lung cancer, which convert smaller cell lung cancer, where there are more.the current first-line treatment of ochitinib drug resistance, 40%-50% of patients drug resistance mechanism is unknown, at the same time the hetic transformation rate of about 15%., therefore, if the first-line application of ochitinib treatment, the second-line treatment options are very limited, from the FLAURA study of the results of 133 patients with first-line Ochitinib treatment failure, 68% of patients can receive second-line treatment, but because of the second-line targeted treatment options are small, so the second-line treatment is not targeted treatment, but the injury of large chemotherapy. this is why first-generation/second-generation drugs are currently being selected for first-line treatment rather than third-generation drugs. I personally believe that in the overall treatment of EGFR sensitive mutation late NSCLC, the first line should choose the first/second generation drug, the third generation drug as a new hope for backline therapy, so that the patient's PFS and OS further extended. for clinicians, we need to apply these drugs rationally and scientifically from the perspective of drug resistance mechanism, combined with the characteristics of each drug, in order to create better efficacy for patients. Dacotinib third-generation EGFR TKI may be the best treatment model for long-term survival for patients Now EGFR TKI has formed a "three generations of the same" situation, I personally think that the "2-plus-three" treatment model is the best model for patients to achieve long-term survival. first in the first-line treatment drug selection, the first and second generation of drugs in the drug resistance mechanism is similar, but the first-line treatment effect is different. in PFS, the second-generation drug dacitinib stands out, with the first-generation PFS reaching 14.7 months, significantly better than the first-generation drug and the second-generation afatinib. , in Chinese groups, the median PFS assessed by the Dacotini researchers was 18.4 months, comparable to the third-generation drug ochitinib. , after dacotinib resistance, theoretically 50% to 60% of patients will have t790M mutation, i.e. more than half of patients can follow up with ochitinib treatment, these patients can be extended after treatment of PFS for about 10 months. , as a result, the "2-3" mode is better than the "1-3" mode. at the archer 1050 study, because the third generation of EGFR TKI is still in development and clinically inadequate, only 9.7% of the patients in the Dacotini group were treated with the third generation of EGFR TKI, with fewer patients receiving Ochtinib. theREFORE, the ARCHER 1050 study is not so much a second-generation drug serialized third-generation drug as a clinical trial of a simple second-generation drug, dacotriib, that gives its advantage. now, with the level of testing and drug accessibility, in an ideal world, after the first-line treatment of Dacotinib resistance, 50% to 60% of patients will be able to receive ochitinib in second-line treatment. in the FLAURA study, 31% of patients in the control group applied ochitinib sequentially, much higher than the ARCHER 1050 study. , therefore, if the ARCHER 1050 study crossed into the FLAURA research era, The T790M mutation-positive patients who failed the first-line treatment of Dacotinib will be able to fully apply the third-generation drug, its "2-3" sequential treatment efficacy data will be more ideal. in the AURA3 study, patients with T790M mutations with first-generation/second-generation drug resistance followed the second-line treatment of Ochitinib, where oS reached 26.8 months, so the second-generation drug serial ochitinib achieved better efficacy. the ARCHER 1050 study, the median OS in the overall population was 34.1 months, the median OS in the Asian population reached 37.7 months, and if in the real world, the third-generation drug ochitini, which is followed by first-line treatment of Dacotin, is certainly more than 40 months. therefore, the key to improving overall efficacy is to enable more patients to apply ochitinib to second-line therapy on the basis of adequate genetic testing. the whole management of EGFR sensitive mutation late NSCLC should pay attention to the "line" of the sequence and "face" of the joint although EGFR TKI is developed according to "generation", but in the EGFR sensitive mutation late NSCLC treatment on the platoon, we should break the "generation" of the sequence treatment model. in fact, the second-generation drug dacotriib was approved after the third-generation ochitinib was listed, and Dacotinib stands out precisely because of its unique advantages. , first, in terms of the mechanism of action, the combination of dacotinib and the target is a common price combination, very strong; dacotinib can significantly reduce the tumor load, thus seeking the opportunity for local treatment. for the drug's platoon, first-line medication can consider the second generation of dacotinib, the theoretical and practical basis is that the first-line treatment in the Chinese group of median PFS more than 18 months, comparable to ochitini first-line treatment, and Dacotini in the tumor remission speed, degree of mitigation and patient quality of life has more advantages. in addition, Ochtinib's drug resistance mechanism is very complex, drug resistance after the option of targeted treatment drugs are very few, about 2/3 of patients can only choose chemotherapy, and chemotherapy basically means that is the last treatment option. if the first-line choice of dacotinib treatment, the second-line patients will still be able to receive ochitinib treatment, and the PFS is further extended by about 10 months, while Ochtinib resistance after the continued chemotherapy as a follow-up treatment option, which means that the first-line choice of Dacotinib treatment can provide patients with more opportunities for backline treatment. therefore, from the perspective of disease management, we should try to use both drugs, so as to bring longer total survival to patients. in addition to the "line" of the sequence, in the treatment should also pay attention to the "face" of the joint. real-world studies have found that EGFR TKI combined anti-angiogenesis therapy or chemotherapy can significantly improve efficacy. , after the patient undergoes targeted treatment, the tumor shrinks, and then local treatment, the patient's survival will be greatly prolonged or even reached the possibility of cure. therefore, first- and second-generation drugs can be used as first-line applications in the field of platooning, with priority given to the use of second-generation drugs, followed by chemotherapy. in the "face" of the expansion, first of all, "target", on this basis, joint or sequential anti-angiogenesis therapy, chemotherapy, local treatment, as a supplement to the back line treatment, for patients to strive for better treatment effect and quality of life. Professor Ma Xuezhen Director of Physicians Doctoral Mentor, Vice President of Qingdao City Center Hospital, Vice President of Qingdao Cancer Hospital, Vice President of Qingdao University Second Annex Hospital, Chairman of the Biological Treatment Committee of Shandong Anticancer Association, Chairman of the Oncology Professional Committee of Qingdao Medical Association, Director of Qingdao Cancer Quality Control Center, Vice President of the Precision Medicine Branch of the Chinese Society of Geriatrics, CSCO, Member of the Committee of the Chinese Society of Clinical Oncology, Member of the Committee of the Chinese Medical Association Association Radiotherapy Branch Standing Committee, Oncology Branch Member, China Research Hospital Association Oncology Branch Standing Committee, Shandong Provincial Clinical Society Vice President, Shandong Medical Association Radiotherapy Branch Vice Chairman, Qingdao Cancer Association Vice President, Shandong Province Key Specialist (Oncology) discipline leader, Qingdao Top Talent, Qingdao Outstanding Discipline Leader, MD Anderson University of Australia Regensburg University Visiting Scholar. source: Tumor information, !-- content display end- !-- determine whether the login ends.
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