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Sotorasib is a small molecular drug that specifically and irreversibly inhibits KRASG12C.
ERK is a key downstream effect factor of KRAS, which can inhibit the growth of KRAS p.G12C tumors in rats for a long time.
preclinical studies have shown that Sotorasib inhibits phosphorylation of extracellular signal-regulating kinases (ERKs).
recently, David S. Hong of the University of Texas Anderson Cancer Center and the Bob T. Li team at the Sloan Kettering Memorial Cancer Center published a paper online in the journal NEJM entitled "KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors" to study the efficacy of KRASG12C inhibitor Sotorasib in treating advanced solid tumors.
: 10.1056/NEJMoa1917239 For patients with advanced solid tumors with KRAS p.G12C mutations, the researchers conducted a Phase 1 clinical trial on sotorasib.
patients take sotorasib ornation once a day.
end point is safety, and the key secondary endpoint is pharmacodynamics and objective mitigation.
follow-up time was 11.7 months.
129 patients were included in the study, including 59 patients with NSCLC, 42 cases of colorectal cancer and 28 patients with other types of cancer.
107 patients (82.9%) stopped treatment;
54 patients (41.9 per cent) had died as of the Data Deadline of 1 June 2020.
3.9 months (0 to 16.6 months) of the medium course of treatment.
treatment for more than 3 months 74 cases (57.4%), 6 months or more 38 cases.
patient characteristics Safety studies did not observe dose-limiting toxicity and no adverse events associated with treatment led to death.
125 patients (96.9%) had adverse events, the most common of which were diarrhea (29.5%), fatigue (23.3%) and nausea (20.9%).
73 patients (56.6%) had treatment-related adverse events and 15 patients (11.6%) had level 3 or 4 adverse events during treatment.
the NSCLC subgroup of 129 patients, 19 patients (32.2%) showed complete or partial remission, 52 patients (88.1%) showed disease control (objective remission or stable condition), and the medium survival period was 6.3 months.
the colorectal cancer subgroup, 3 patients (7.1%) were objectively relieved, 31 patients (73.8%) were under control, and the medium survival was 4.0 months.
with pancreatic, endometrial, appendicoma and melanoma were also relieved.
the efficacy of Sotorasib in the NSCLC subgroup, Sotorasib showed encouraging anti-cancer activity in patients with advanced solid tumors with treated KRAS p.G12C mutations, but with some toxic side effects.
clinical trials to evaluate Patients with Sotorasib who treat non-small cell lung cancer or other solid tumors alone or in combination with multiple drugs are ongoing.
resources: s1. KRASG12C Addion with Sotorasib in Advanced Solid Tumors.