ASCO 2020: MEK162 (Bemetinib) Joint Imatinib Treatment of Advanced Gastrointestinal Interside Tumor phase II Clinical Study

BACKGROUND: ETV1 and KIT are the main transcription factors and signal survival factors of the family of gastrointestinal mesotheliomaIn the preclinical model, BINI inhibited ETV1 and Imatinib inhibited KIT in inhibition of gastrointestinal mesoplasmic tumor development and development has synergiesThis single arm Phase II study was designed to test the efficacy of bemetinib and imatinib as a first-line treatment for patients with advanced gastrointestinal mesotheliomamethod: Untreated adult patients with advanced gastrointestinal mesothelioma received Imartinibinib (400mg per day) gabemetinib (30mg twice a day) for 28 daysThe primary endpoint (EP) is the objective mitigation rate (ORR) under the RECIST 1.1 standard (full mitigation of the (CR) and partial mitigation (PR)) the study was designed to detect a 20% improvement in ORR in Imatinib alone (an unacceptable rate of 45% and an acceptable rate of 65%)Using a precise two-way test, the one-sided type I error was 0.08 and the type II error was 0.1, requiring a sample size of 44 patientsMore than 24 patients reachPR and can be judged to be effectiveSecondary endpoints are RR, remissable conversion rate (RCR), no progression lifetime (PFS), total lifetime (OS) and long-term adverse events, based on The Choi and EORTC standardsCorrelation tests were performed on epigenetic genomics of MSK-IMPACT, cfDNA detected by MSK-ACCESS, level of ETV1 protein and transcription altimelime, and signal conduction inhibitionresults: 38 of the 39 patients with gastrointestinal mesothelioma were evaluated at the end of the data on January 31, 2020, including 3 KIT/PDGFRA wild patientsThe median age is 60 years (range 29-78) and the proportion of women is 29%26 of the 38 patients confirmed to have reached PR, the best ORR was 68.4% (95% CI on both sides, 51%-83%; 90% CI on one side, 57%-100%)In 8 of the 9 patients, it was cut after treatment, and RCR was 88.9% (95% CI, 52-100%)There are still 13 patients in trial observation (2 to 159 weeks)Nine patients were suspended (11-159 weeks) due to progression of the disease, and one patient progressed within 3 months, showing primary resistanceLevel 3/4 toxicity includes elevated CPK (asymptomatic, 61%), neutrophil reduction (11%), plaque (8%), and anemia (8%)No accidental toxicity was observedSubsequent reports will describe the correlation between MSK-IMPACT, MSK pathways, and pairs of tumor biopsiesconclusion: The study reached its main endpointBemetiniega Imatinib is very effective in untreated advanced gastrointestinal mesothelioma, and long-term treatment-related toxicity can be controlledIn the first-line treatment of gastrointestinal mesothelioma, this joint strategy is worth evaluating further when compared directly with Imatinibauthor: Medical Forum Network Source: medical forum.com