Biliary tract cancer

The Lancet, Journal Year: 2021, Volume and Issue: 397(10272), P. 428 - 444

Published: Jan. 1, 2021

Language: Английский

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Trends in kinase drug discovery: targets, indications and inhibitor design

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(11), P. 839 - 861

Published: Aug. 5, 2021

Language: Английский

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Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial

The Lancet Oncology, Journal Year: 2021, Volume and Issue: 22(5), P. 690 - 701

Published: March 31, 2021

Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence available for second-line chemotherapy. The aim of this study was to determine benefit derived from FOLFOX (folinic acid, fluorouracil, oxaliplatin) in advanced cancer.

Language: Английский

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Cholangiocarcinoma

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: Sept. 9, 2021

Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. Each anatomic subtype has distinct genetic aberrations, clinical presentations therapeutic approaches. In endemic regions, liver fluke infection associated with CCA, owing to oncogenic effect chronic biliary tract inflammation. other CCA inflammation choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. Administration anthelmintic drug praziquantel decreases risk from flukes, reinfection common future vaccination strategies may more effective. Some patients are eligible for potentially curative surgical options, such resection transplantation. Genetic studies provided new insights into pathogenesis two aberrations that drive non-fluke-associated intrahepatic fibroblast growth factor receptor 2 fusions isocitrate dehydrogenase gain-of-function mutations, therapeutically targeted. desmoplastic cancer targeting tumour immune microenvironment might promising approach. remains disease further scientific needed improve patient outcomes. system often This Primer reviews epidemiology, pathophysiological mechanisms, diagnosis management cholangiocarcinoma, highlights experience directions.

Language: Английский

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ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group

Annals of Oncology, Journal Year: 2022, Volume and Issue: 33(8), P. 750 - 768

Published: July 6, 2022

•Validated and sensitive ctDNA assays can be used to genotype advanced cancers select patients for targeted therapies.•Initial genotyping with should considered when rapid results are needed, tissue is unavailable.•ctDNA assay limited by false-negative results, lower sensitivity fusion events copy number changes.•Use of detect molecular residual disease not recommended, due lack evidence its clinical utility. Circulating tumour DNA (ctDNA) conducted on plasma rapidly developing a strong base use in cancer. The European Society Medical Oncology convened an expert working group review the analytical validity utility assays. For cancer, validated adequately have identifying actionable mutations direct therapy, may routine practice, provided limitations taken into account. Tissue-based testing remains preferred test many cancer patients, detecting changes, although routinely faster will clinically important, or biopsies possible inappropriate. Reflex following non-informative result, testing. In treated early-stage cancers, detection relapse, has high anticipating future relapse cancers. Molecular disease/molecular cannot recommended as currently there no directing treatment. Additional potential applications assays, under research development include responding therapy early dynamic changes levels, monitoring resistance before progression, screening asymptomatic people Recommendations reporting made.

Language: Английский

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Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation

JAMA Oncology, Journal Year: 2021, Volume and Issue: 7(11), P. 1669 - 1669

Published: Sept. 24, 2021

Importance

Isocitrate dehydrogenase 1 (IDH1) variations occur in up to approximately 20% of patients with intrahepatic cholangiocarcinoma. In the ClarIDHy trial, progression-free survival as determined by central review was significantly improved ivosidenib vs placebo.

Objective

To report final overall (OS) results from which aimed demonstrate efficacy (AG-120)—a first-in-class, oral, small-molecule inhibitor mutant IDH1—vs placebo for unresectable or metastatic cholangiocarcinoma withIDH1mutation.

Design, Setting, and Participants

This multicenter, randomized, double-blind, placebo-controlled, clinical phase 3 trial conducted February 20, 2017, May 31, 2020, at 49 hospitals across 6 countries among aged 18 years older withIDH1mutation whose disease progressed prior therapy.

Interventions

Patients were randomized 2:1 receive ivosidenib, 500 mg, once daily matched Crossover permitted if had progression radiographic findings.

Main Outcomes Measures

The primary end point blinded independent radiology center (reported previously). Overall a key secondary point. analysis OS followed intent-to-treat principle. Other points included objective response rate, safety tolerability, quality life.

Results

Overall, 187 (median age, 62 [range, 33-83 years]) randomly assigned (n = 126; 82 women [65%]; median 61 33-80 61; 37 [61%]; 63 40-83 years]); 43 crossed over ivosidenib. reported elsewhere. Median 10.3 months (95% CI, 7.8-12.4 months) 7.5 4.8-11.1 (hazard ratio, 0.79 [95% 0.56-1.12]; 1-sidedP .09). When adjusted crossover, 5.1 3.8-7.6 months; hazard 0.49 0.34-0.70]; < .001). most common grade higher treatment-emergent adverse event (≥5%) both groups ascites (11 [9%] receiving 4 [7%] placebo). Serious events considered related (2%). There no treatment-related deaths. apparent decline life compared

Conclusions Relevance

found that well tolerated resulted favorable benefit placebo, despite high rate crossover. These data, coupled supportive data tolerable profile, advanced

Trial Registration

ClinicalTrials.gov Identifier:NCT02989857

Language: Английский

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Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Annals of Oncology, Journal Year: 2022, Volume and Issue: 34(2), P. 127 - 140

Published: Nov. 10, 2022

Language: Английский

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Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(5), P. 708 - 724.e11

Published: April 2, 2021

Language: Английский

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Futibatinib for FGFR2 -Rearranged Intrahepatic Cholangiocarcinoma

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(3), P. 228 - 239

Published: Jan. 18, 2023

Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with poor prognosis. Futibatinib, next-generation, covalently binding FGFR1-4 inhibitor, has been shown to both antitumor activity patients FGFR-altered tumors and strong preclinical against acquired resistance mutations associated ATP-competitive FGFR inhibitors.In this multinational, open-label, single-group, phase study, we enrolled unresectable or metastatic FGFR2 fusion-positive rearrangement-positive cholangiocarcinoma disease progression after one more previous lines of systemic therapy (excluding inhibitors). The received oral futibatinib at dose 20 mg once daily continuous regimen. primary end point was objective response (partial complete response), assessed by independent central review. Secondary points included the duration, progression-free overall survival, safety, patient-reported outcomes.Between April 16, 2018, November 29, 2019, total 103 were futibatinib. A 43 (42%; 95% confidence interval, 32 52) had response, median duration 9.7 months. Responses consistent across patient subgroups, including heavily pretreated disease, older adults, who co-occurring TP53 mutations. At follow-up 17.1 months, survival 9.0 months 21.7 Common treatment-related grade 3 adverse events hyperphosphatemia (in 30% patients), an increased aspartate aminotransferase level 7%), stomatitis 6%), fatigue 6%). Treatment-related led permanent discontinuation 2% patients. No deaths occurred. Quality life maintained throughout treatment.In previously treated fusion use futibatinib, covalent measurable clinical benefit. (Funded Taiho Oncology Pharmaceutical; FOENIX-CCA2 ClinicalTrials.gov number, NCT02052778.).

Language: Английский

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Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2021, Volume and Issue: 6(10), P. 803 - 815

Published: Aug. 3, 2021

Language: Английский

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