Crizotinib for the treatment of anaplastic lymphoma kinase

Crizotinib is used to treat anaplastic lymphoma kinase


Rr, director of the Office of Oncology Products, Center for Drug Evaluation and Research, said that the approval of crizotinib and supporting diagnostic methods has made clinical Patients who are more likely to respond to the drug can be selected. Targeted therapies such as crizotinib are important options for treating this disease.
Fusion genes can be found in a variety of tumors, such as anaplastic large cell lymphoma, inflammatory myofibroblastoma, and neuroblastoma. They are caused by insertion of the short arm of chromosome No. 1. Depending on the gene breakpoint, there are at least one type of fusion gene. The fusion gene is transmitted through the activation of downstream substrate molecules, and various transduction pathways overlap with each other, forming an intricate signal transduction network that affects cell proliferation, differentiation, and apoptosis. The fusion gene binds the kinase regions of the two molecules to each other through the extracellular helical domain of the fusion partner to form a stable dimer, which activates downstream // and other pathways through autophosphorylation, thereby causing the malignant transformation of cells.
Preliminary epidemiological studies show that among patients, the positivity rate is approximately %~%, which means that there are approximately 10,000 positive patients in the United States every year, and it is estimated that 10,000 patients are diagnosed as positive every year globally. For positive patients, crizotinib showed significant therapeutic activity and prolonged patient survival. Crizotinib is a small molecule inhibitor. The approval of crizotinib was based on two clinical safety and efficacy data that included a total of 2 positive patients with locally advanced or metastatic disease.
The two multicenter single-arm clinical trials include the r population expansion (r) portion of a phase 1 clinical trial (R) and a phase 1 clinical trial (R). In the R study, according to the investigator's assessment, the objective response rate (RR) of the crizotinib group was %, including 9 complete responses and 2 partial responses. The median treatment time was weeks, and the objective response rate of % was reached at 10 weeks of treatment. Median duration of response was weeks. []
In the R study, 10 patients from countries with positive advanced disease who failed previous chemotherapy (% of patients had received at least more than 1 chemotherapy regimen) were treated with crizotinib. According to the investigator’s evaluation, The RR is %, including complete remission and partial remission. The median treatment time is weeks. The objective response rate of % is reached at the treatment week. The median duration of response is weeks.
The most common adverse reactions (%) observed in both studies were visual impairment, nausea, diarrhea, vomiting, edema, and constipation. Grade 1 and grade 1 adverse reactions, including increased alanine aminotransferase and neutropenia, were reported in at least % of patients in both studies.
Another retrospective study of existing survival data showed that for patients who tested positive and received crizotinib treatment, the annual survival rate was %, and the annual survival rate was %. There is no significant correlation between the patient's survival time and his/her gender, race, smoking history or age.
Also approved at the same time as crizotinib was the first supporting genetic diagnostic method Br r using fluorescence in situ hybridization, which is a method used to detect fusion genes in global clinical trials. The test will help identify patients who may benefit from treatment with crizotinib.

Address: Zhongguancun Building, Beisihuan Middle Road, Haidian District, Beijing
Company name: Beijing Mingkang Trading Co., Ltd.
Telephone:
Number:
Contact Person: Miss Chen