Current and trends in targeted treatment of lung cancer - fine, joint, overcoming drug resistance and brain metastasis

In recent years, the targeted treatment oflung cancerhas developed rapidly, and the first-line treatment options and drug-resistant treatment strategies for patients with EGFR mutation-positive non-small celllung cancer(
NSCLC) are equally concerningIn particular, Professor He Yong of the Army Special medical center was invited to share with us the current situation and trends ofthe targeted treatment oflung cancer, the fullmanagementexperience of patients with EGFR mutation-positive NSCLCHe Yong, Professor, Chief Physician, Doctor's Mentor, Director of Respiratory Medicine at the Army Military Medical Characteristics Center (Daping Hospital), Member of the Lung Cancer Committee of the Respiratory Physicians Branch of the Chinese Physicians Association, Chairman of the Respiratory Committee of the Chinese and Western Medical Association of Chongqing, Deputy Chairman of the Respiratory Committee of the Chongqing Medical Association, Vice President of the Respiratory Physicians Branch of Chongqing Medical Association, Deputy Director of TheManagementAssociation of China Medical Education, Standing Member of the Oncology Professional Committee, Standing Committee of the CancerImmunology Therapy Committee of the Chinese Medical Education Association, editorial board of the Lancet Respiratory Medicine, JCO, Chinese edition, etc., obtained the National Natural Science Fund's topics 5, 863 major projects, etc., published a number of SCI papers .
The current situation and trends of lung cancer targeted therapy - fine, joint, overcome drug resistance and brain metastasis targeted therapy has brought great good news to the vast number of patients with advanced lung cancer, and there have been many research advances at this year's annual meeting of the American Clinical Oncology Society (
ASCO ), the World Lung Cancer Congress (WCLC), and the European Society of Oncology (ESMO), especially in driving genes First, in addition to driver genes such as EGFR and ALK, we have found other targets, the current National Integrated Cancer Network (NCCN) guidelines ROS1, NTRK also as a recommended target, the second category of recommendations have RET, c-MET and HER2 targets, in addition to some of the rarer targets, such as NGR1, KRAS, etc., for these treatment targets, there will be more new targets for cancer patients Second, targeted therapy is no longer limited to the use of only one targeted drug, research is more joint drugs, such as targeted therapy and chemotherapy, with anti-
avascular -generation drugs and radiotherapy combined to further improve the treatment effectiveness of lung cancer patients Third, in terms of drug resistance mechanism, whether first-line application or backline application of EGFR TKI drug resistance mechanism, there are more research is under way In addition, the adverse reactions of these targeted drugs and the ability to treat brain metastasis or enter the blood-brain barrier have also become the focus of researchers' attention How to develop some adverse reactions lower, and can overcome brain metastasis of targeted drugs, will become an important trend in the future development EGFR mutation-positive late NSCLC patients in the first-line treatment choice considerations and full planning management NCCN guidelines have Oxitinib as the eGFR sensitive mutation of late NSCLC as the preferred recommendation of first-line treatment, in August this year, the domestic also approved Oxitini's first-line treatment adaptation certificate, to the vast number of patients and medical workers brought the gospel, but also for Oxitini's first-line applications brought more protection face first-, second-generation, third-generation EGFR TKI, in the choice of EGFR mutation-positive late NSCLC first-line treatment, what questions should we consider? First, we need to consider progression-free survival (PFS), second, total survival (OS), third, adverse reactions, the ability to overcome brain metastasis, and the ability to benefit more patients From PFS, pfS in the first generation of EGFR TKI is around 11 months, the second generation eGFR TKI afatinib, although compared to the first generation of drugs, its PFS shows a statistical advantage, PFS rate and OS rate is higher than the first generation of drugs, but PFS is also about 11 months, the second generation EGFR TKI Dacostini, despite achieving 14.7 months of PFS, has crossed both sides of its survival curve from the OS and has not seen a significant survival benefit among the Asian population, while the three generations of EGFR TKI Ohitini have a PFS of 18.9 months, the longest PFS in the field of EGFR TKI In addition, in the FLAURA study, the Ochtinib group benefited from survival, reporting 38.6 months of OS data at this year's ESMO conference, even though second-line cross-applications of Theochtinib were allowed to be applied to patients with a positive T790M mutation after the control group progression Second, for brain transfer patients, the first- and second-generation EGFR TKI is not easy to enter the blood-brain barrier, and Oxitinib can accumulate in the skull, brain metastasis has a good control effect, in the course of treatment, the probability of brain metastasis will be reduced Third, the incidence of adverse reactions of second-generation EGFR TKI afatinib and dacostinib was higher, the proportion of dose adjustment due to adverse reactions was also higher, about 40% to 60%, and the proportion of dose adjustment in the third generation eGFR TKI Oxitinib due to adverse reactions was only 5% to 6% So from the adverse reaction point of view, Oxitinib in the EGFR mutation-positive NSCLC first-line application is a very good choice Fourth, from the benefit of the population, if the first-generation or second-generation EGFR TKI, a large proportion of patients will have difficulty receiving Oxitinib treatment on the second line Theoretically, about 40% to 50% of patients can receive Oxitinib treatment on the second line, but in real-world studies, this figure is only about 25%, in clinical studies, the proportion will be lower, only about 10% And if the three generations of EGFR TKI Ohtinib are applied directly to the front line, most patients can be guaranteed better survival benefits oxitinib drug resistance, should be based on different drug resistance mechanisms to take different treatment strategies
concerned about whether Oxitinib drug resistance after the method of overcoming drug resistance, with our understanding of drug resistance mechanism, the follow-up has the corresponding response strategy In clinical studies, we found that 20% to 30% of patients were able to overcome drug resistance with targeted therapy if they understood the drug resistance mechanism of Oxitinib Although we do not know enough about oxitinib's drug resistance mechanisms, we actually know some of these mechanisms, such as the loss of T790M, have a very large impact on Oxitini's drug resistance In patients with T790M mutations still present, most of them will experience re-mutations in the EGFR kinase domain, and patients with T790M loss will have bypass activation more often In patients with EGFR kinase domain mutations, if there is a C797S triple mutation, or g724S, G719X secondary insertion mutation, we can adopt appropriate methods to overcome drug resistance, such as C797S triple mutation patients, we can take the bugatinib combined with situsione monoantigen We've seen a lot of case reports, and our team has conducted a cohort study of about a dozen patients, and found that bugatinib, in combination with citoxil to treat Patients with C797S triple mutation, can get PFS for more than 1 year, while chemotherapy can only get about 3 months of PFS For some patients with other mutations, such as the G724S mutation, we can use afatinibini to overcome drug resistance For patients with bypass activation, such as c-MET amplification, oxidine-combination cedinib therapy can be applied In addition, there are recent new drugs, such as Tepotinib and JNJ-372, that can also overcome resistance caused by c-MET amplification For patients with RET fusion and ROS fusion, LOXO-292 and BLU-667 can be used to overcome Oxitinib resistance and target combination, so patients can still obtain longer PFS or disease control The emergence of new target drugs provides greater possibilities for target joint overcoming drug resistance In addition, we also note that patients may develop small cell lung cancer conversion after Oxitinib resistance, in addition to blood testing, we also need to pay attention to tissue biopsies, for patients who find small cell lung cancer conversion, can be overcome by chemotherapy Of course, we can not ignore the traditional treatment methods such as radiotherapy, anti-
angiogenesis the comprehensive application of the disease in patients, give full play to the role of each treatment, in order to bring the greatest benefit to patients author: Oncology Information Source: