Lancet Oncol: Ivosidenib significantly improved survival rates in patients with advanced mIDH1 bile tube cancer

Tibsovo (Ivosidenib) Avonib (AG-120), is an oral, powerful inhibitor targeting mutations in iso-citric acid dehydrogenase 1 (IDH1).
and IDH1 mutations occur in a variety of tumors.
was approved by the FDA on July 20, 2018 and marketed by Agios Pharmaceuticals under the name Tibsovo, which was approved for the treatment of adult patients with recurring or refraortic acute myeloid leukemia (R/R AML), becoming the first FDA-approved R/R AML drug to treat IDH1 mutations.
is Chinese mainland to authorize Keystone Pharmaceuticals to promote it.
, May 13, 2020 The Lancet Oncology published a paper on the progress of Ivosidenib (AG-120) in the treatment of IDH-1 mutations in chemotherapy. Positive results obtained from ClareDHy in the Lll phase clinical trial significantly increased patients' progressity-free survival (PFS) by 2.7 months, extended OS to 10.8 months, and reduced the risk of disease progress or death by 63%.
previous results were also partially published in 2019 ESMO, see: 2019 ESMO: Ivosidenib significantly improved survival rates in patients with advanced mIDH1 bile dud cancer, a multi-center, randomized, double-blind, placebo-controlled multi-center study.
patients with bile tube cancer were admitted to the group: bile tube cancer patients had received 1-2 systemic treatments; Bile tube cancer patients showed R132C, 171 (92%) bile tube cancer patients also had metastatic disease, 86 (46%) bile tube cancer patients have received two previous treatments.
patients with bile tube cancer were randomly divided into ivosidenib group (124) and placebo group (61) on a 2:1 scale.
patients with bile tube cancer in the ivosidenib group were treated with oral 500 mg ivosidenib per day;
The main study endpoints of the trial were progress-free lifetime (PFS), and the secondary study endpoints were total lifetime (OS), objective response rate (ORR), reaction duration and reaction time (assessed by researchers and research centers);
the main endpoint PFS, the ivosidenib group: the placebo group was 2.7 months: 1.4 months (HR-0.37, 95% CI:0.25-0.54, p-lt;0.001).
six-month progressed survival rate of 32 percent of patients with bile tube cancer in the Tibsovo group and 22 percent of 12 months of progress-free survival.
survival rate of 2.7 months reduced the risk of death by 63% in patients with bile tube cancer.
is comforting for patients with bile tube cancer who are treated with more than one line of treatment.
test results (Tibsovo vs. placebo group): in the middle total lifetime OS, ivosidenib group: placebo group was 10.8 months: 9.7 months (HR s 0.69, 95% CI: 0.44-1.10, p s 0.06).
data from the ivosidenib group were not significantly different from those in the placebo group because 35 patients in the 61 placebo group had oral ivosidenib treatment in the latter stages, so the placebo group showed higher OS.
If it is assumed that some patients in the placebo group were not treated with Tibsovo, model analysis showed that the middle OS in the placebo group was only 6 months (HR=0.46, 95% CI: 0.28-0.75, p<0.001).
6 months OS is 67% and 12 months OS is 48%.
end point: disease control rate: 53% vs 28%.
ORR: 2% vs 0%, don't look at this data is low, but because its mechanism of action is somewhat similar to Soraphinib's treatment of advanced liver cancer, which benefits the patient's survival by preventing tumor progression (inhibiting tumor cell proliferation and allowing the patient to achieve a basically stable state), which is a good explanation why the drug's DRR is not low.
duration: 2.6 months (IQR 1.4-6.0) vs 1 6 months (1.1-2.7) 3 levels and above Adverse event rates: 30% vs 22%.
common adverse reactions are mainly nausea, diarrhea, fatigue, cough, etc. , the extension of QT period on the electrostat map seems to be a relatively specific adverse reaction.
better treatment groups in terms of the quality of life reported by patients.
patients with bile tube cancer experienced a significant decrease in quality of life about 1 cycle after receiving the intervention, while the quality of life decreased less in the treatment group.
NCCN guidelines have been updated to include Ivosidenib in second-line treatment for patients with mIDH1 bile tube cancer.