Bile tube cancer is again targeted for new drugs: Ivosidenib and Binimetinib are highly effective.

Intra-liver bile tube cancer is a highly heterogeneous, invasive cancer, its prognosis is poor, the five-year survival rate is less than 10%, for can not be removed or metastatic bile tube cancer, Gissithambin combined cisplatin chemotherapy has been the standard treatment.
Since the first bile tube cancer target drug pemigatinib was officially launched to end the era of bile-gallbladder tumor-only chemotherapy, the targeted drug has once again seen hope in patients with bile-gallbladder tumors, and the research firepower of bile-throb tumor-targeted drugs has been fully developed.
to introduce you today to two new drugs, Ivosidenib and Binimetinib.
Ivosidenib is a powerful oral targeted inhibitor for IDH1 mutations, and the Lancet magazine recently revealed Ivosidenib's remarkable efficacy in the stage stage of bile tube cancer clinical trial Clare Dhy.
The ClareDHy trial was a multi-center, randomized, double-blind, placebo-controlled multi-center lll clinical study.
a total of 185 patients with bile tube cancer who received 1-2 systemic treatments but developed the disease and carried mutations in the IDH1 gene were randomly divided into Ivosidenib (124) and placebo groups (61) by a 2:1 ratio.
500 mg Ivosidenib daily in patients with bile tube cancer in the Ivosidenib group, and oral placebo daily in patients with bile tube cancer in the placebo treatment group.
results were better: 1, medium PFS (no progression lifetime) Ivosidenib group: placebo group: 2.7 months: 1.4 months (HR s 0.37, 95% CI: 0.25-0.54, p.lt;0.001).
reduced the risk of death by 63%, which is a good number for patients with bile tube cancer who have received treatment above the first line.
2, Medium OS (Total Lifetime) Ivosidenib Group: Placebo Group : 10.8 months: 9.7 months (HR: 0.69, 95% CI: 0.44-1.10, p , 0.06).
data from the Ivosidenib group were not significantly different from those in the placebo group, as 35 patients in the 61 placebo group had oral Ivosidenib treatment in the latter stages of the group.
If patients with bile tube cancer in the placebo group had been taking oral placebos, a 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.lt;0.001).
3, DCR (disease control rate) Ivosidenib group: placebo group : 53% : 28%.
Ivosidenib was significantly superior to the placebo group.
4, ORR (objective mitigation rate) Ivosidenib group: placebo group : 2% : 0%.
Ivosidenib stabilizes patients with bile tube cancer by inhibiting tumor cell proliferation, preventing tumor progression.
2% may seem low, but Ivosidenib has a disease control rate of 53%.
5, Medium Duration Ivosidenib Group: Placebo Group : 2.6 months (IQR 1.4-6.0): 1.6 months (1.1-2.7).
6, in terms of safety, adverse events (TEAEs) that occur during treatment in the Ivosidenib group include nausea (32.1%), diarrhea (28.8%), fatigue (23.7%), Cough (19.2%), abdominal pain (18.6%), abdominal water (18.6%), decreased appetite (17.3%), anemia (16.0%), vomiting (16.0%).
46 per cent in the Ivosidenib group, 36 per cent in the placebo group, and 46 per cent in the untreated related deaths.
Binimetinib Binimetinib is a powerful, highly selective MEK1/2 variant inhibitor, and the MEK protein is an upstream regulatory factor pathway for extracellular signal-related kinases (ERKs).
preclinical studies have shown synergy between biscarbonate and chemotherapy for bile thyme tumors.
The clinical trial is an open, one-arm phase IB study designed to evaluate patients with first-line gysythathambine in the second- and third-line treatment of bile tube cancer with bilibromation, designed for dose increment and queue expansion.
the study included 34 patients, of which 9 were in the dose increment group and 25 in the queue expansion group, of which 25 patients (73.5%) were treated first-line and 9 patients (26.5%) were treated with second-line treatment.
also had 29.4% gallbladder cancer (n s 10), 29.4% (n s 10), 26.5% (n s 9) and 14.7% (n s 5) for cervical bile cancer.
results: 1, ORR: 20.6% (95% CI, 7.0-34.2).
2, DCR: 76.5% (95% CI, 62.2-90.8).
7 patients (20.6%) and 19 patients (55.9%) showed partial remission and disease stabilization, respectively.
3, mPFS: 4.1 months (95%CI, 2.8-5.7), 3 months PFS rate of 64.0%, 4, mOS: 7.8 months (95% CI, 5.9-12.2) in the logo In terms of materials, patients with abnormal activation of the RAS/RAF/MEK/ERK signal path showed longer PFS (5.4 months vs 2.6 months, P=0.031) and OS (10.8 months vs 5.3 months, P=0.011).
major adverse reactions are controllable anemia and fatigue.
the treatment program has shown effective therapeutic efficacy in bile tube cancer, especially in patients with bile tube cancer with abnormal activation of RAS/RAF/MEK/ERK signaling pathlines.
bile tube cancer is a cancer with a high degree of malignancy in China, with relatively poor prognosmation and limited treatment.
that there has been more and more research on targeted drugs in recent years, and we expect new treatment models to change the future and rewrite the guidelines.
source: 1.Abou-Alfa, G. K. et al. Ivosidenib in IDH1-mutant, processy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3. study. Lancet Oncol. (2020) doi:10.1016/S1470-2045 (20)30157-1. 2.Kim ST, Kang JH, Lee J, et al. Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. Ann Oncol. 2019. 30(5): 788-795.