Professor Cao Wei: Avapritinib Drug-resistant Mutation, GIST Patient Treatment To a New Heights

Gastrointestinal mesoplinoma(GIST) is mainly caused by GENE mutations driven by KIT and PDGFRA, and surgery is a fundamental treatment for limited GISTGIST is insensitive to chemotherapy, and Imatinib pioneered the era of GIST targeted therapyHowever, patients with certain primary mutations, such as PDGFRA exosome 18 mutations, are less sensitive to existing standard targeted drugs, especially those with D842V mutationsIn the course of imatinib or second- and third-line targeted drug therapy, secondary mutations can lead to drug resistance, so the search for drug resistance mechanisms, the development of new drugs has become a concern of researchersIn early 2020
FDAapproved Avapritinib's listing for the treatment of adult patients with PDGFRA exosome 18 mutations that are non-surgical or metastatic GIST, bringing a life-changing life for this segment of patientsIn addition, the drug also has a better inhibitory effect on other PDGFRA mutations and KIT secondary mutationsGiST tumor genotype to the guiding significance of treatment
gastrointestinal interstitial tumor (GIST) is the most common gastrointestinal inter-intestinal leaf tumor, with epithelial sources ofstomach cancerand bowel cancer, the pathogenesis is now clear, mainly by KIT and PDGFRA gene mutationcause of Gene test results are very important todiagnosisGIST, and also play a very important role in the treatment and prognosis of GIST, so the genotype of GIST is getting more and more attention, whether it is first-line treatment, second-line treatment or third-line treatment, are based on the risk classification based on reference to the genotype to develop the best treatment strategy Some special types, such as PDGFRA gene mutation patients, its targeted treatment in the past there are some limitations, until early 2020 FDA approval of Avapritinib for PDGFRA exosome 18 mutation patients, especially D842V mutation patients, the effect is very significant, so far to reverse the PDGFRA MUTATION patients poor prognosis and no effective drugs available embarrassing situation Therefore, according to different genotypes, precision targeted treatment, is now and in the future the direction of the development of GIST treatment, the role of genotype will be more and more important the problems and challenges that surgeons face in the of GIST surgery is the only cure for surgical GIST patients For patients with recurrent metastasis GIST, targeted drug therapy plays a very important role in prolonging survival, how to effectively combine targeted drug therapy with surgery, carry out effective, reasonable and scientific precision treatment, is the common goal of clinicians engaged in GIST diagnosis and treatment As far as surgeons are concerned, there are many challenges in the GIST treatment process As we all know, GIST is prone to relapse and metastasis, especially in the process of targeted treatment due to the progress of drug resistance, patients need repeated operations, which is a huge challenge for surgeons, this challenge is due in part to the need for surgeons to have a comprehensive judgment and analysis of the disease, on the other hand, from the surgeon's own and the team as a whole surgical ability, risk awareness and other factors Therefore, how to correctly judge the progress of disease in the treatment of GIST patients, how to carry out surgical intervention, has always been a challenge for surgeons from a surgeon's point of view, successful surgery is important, but more and better medications are equally important, such as first-line imatinib, second-line Shoneib
and third-line rigofenib, all of which have benefited from varying degrees of survival in progressive GIST patients We want more effective and precise medications for patients with specific genotypes, and surgeons and physicians are expecting new drugs as well In addition, in the process of drug use, the whole process of management is also very important, to understand the various drug adaptation evidence, correct use methods and adverse reactioncontrol, these are GIST clinicians, but also surgeons in practice, is a problem that needs to be solved through serious study Avapritinib's approval for the future development of GIST treatment Avapritinib is the new GIST targeted drug that has been approved by the FDA for the treatment of PDGFRA exnoon 18 mutant GIST, especially in patients with D842V mutations, providing new survival opportunities for such patients As clinicians, it is highly anticipated that these drugs will continue to be introduced to the clinic, as patients with advanced and non-surgical PDGFRA exosome 18 mutations are very clearly recommended for the full use of Avapritinib On this basis, we also look forward to Avapritinib's ability to develop complementary and new complementary treatments in these GIST patients to explore the maximum survival benefits for these patients Because PDGFRA exosome 18 mutant GIST surgery, due to immatteriniborine or other targeted drugs, it is not possible to perform effective preoperative and postoperative systemic treatment, especially in some patients with pDGFRA mutations at high risk of recurrence Now that the new drug Avapritinib is available, we are considering that patients with a specific pDGFRA mutation with a specific typepcanie can try Avapritinib's new complementary therapy and assistive therapy to maximize the effects of this very effective drug and benefit patients The results of our recent global multicenter clinical studies, as well as the results of clinical studies in previous meetings, confirm this feasibility Most of the patients with KIT mutation will develop secondary drug resistance in the course of treatment, such as KIT 11 exoon secondary onset 17 or 18 exome mutation, resulting in the kinase conformation itself life-changing change, resulting in type II TKI loss of therapeutic effect The new drug Avapritinib is type I TKI, which overcomes the disadvantages of type II TKI's inability to inhibit the active state of kinase conformation, and can effectively bind to mutant proteins to overcome drug resistance We very much hope that the results of the study will be published as soon as possible in the subgroup of Avapritinib in PATIENTs with KIT secondary drug resistance, which means that the drug resistance problem will be addressed in some PATIENTs with THE following TYPE of KIT secondary mutation, so that clinicians can choose the appropriate drug treatment based on the patient's specific genetic mutation type Overall, the new drug will lead to treatment advances for GIST patients, and as surgeons are eager for new drugs to be introduced, more treatment options will benefit patients Source: Cancer Information