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Treatment Options for Advanced Cholangiocarcinoma
Farshid Dayyani, MD, PhD | FRIDAY, FEB. 28th 2020
Epidemiology • 3 Subtypes: • intrahepatic, perihilar, and distal
• Incidence 1.2/100,000 per year in U.S.
• 3% of GI cancers , but accounts for 20% of deaths from hepatobiliary cancers (median OS about one year)
• Rising incidence from 2001 – 2015• NASH, Hep C, Cirrhosis
• Only curative option is resection, but 2/3 diagnosed at advanced stage
Gemcitabine/Cisplatin in 1L advanced Cholangiocarcinoma: ABC-02 Trial
PR= 45%, DCR 84%
PFS= 11.8 mo
OS= 19.2 mo
ABC-06: second–line mFOLFOX vs active symptom control
Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium
Molecular characterization of cholangiocarcinoma
Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium
Targeted Therapy for Biliary Tract Cancers
Presented By William Harris at 2019 ASCO Annual Meeting
The IDH family of enzymes:
cytoplasm and peroxysomes (IDH1) mitochondria (IDH2 and IDH3) involved in a number of cellular processes
• mitochondrial oxidative phosphorylation
• glutamine metabolism• Lipogenesis• glucose sensing• regulation of cellular redox status
Targeting IDH1 population (ClarIDHy)
Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium
ClarIDHy Trial: Overall Survival
1. Abou-Alfa et al. Presented at: 2019 ESMO Congress; September 27 to October 1, 2019; Barcelona, Spain. Abstract LBA10_PR. 2. Faivre et al Ann Oncol 2017. 3. Yao et al J Clin Oncol 2016
FIGHT-202: a phase 2 study of pemigatinib in patients with previously treated locally advanced or metastatic CCA
Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz3
FIGHT-202: Response and Survival Cohort A
Targeted Therapy in Molecularly-Altered Advanced Cholangiocarcinoma
Ivosidenib1 Infigratinib2 Pemigatinib3 Dabrafenib + Tremetinib4
N 124 71 107 35
Target IDH FGFR FGFR BRAF
ORR 2% 25.4% 35.5% 36%
DCR 53% 83.6% 82% 75%
mPFS 2.7 months 6.8 months 6.9 months 9.2 months
mOS 10.8 months 12.5 months 21.1 months 11.7 months
Figure Adapted From:1Abou-Alfa et al ESMO 2019; 2 Javle et al ESMO 2018 3Vogel et al ESMO 2019; 4Wainberg et al ASCO GI 2019
Other promising targets not to overlook in BTC
Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium
Locoregional Treatment in Advanced IHC
Locoregional Treatment in Advanced IHC
Clinical Trial Currently Enrolling at UC Irvine:1. UCI 19-20 - A Phase III Randomized, Double-Blind, Placebo-Controlled, Multi-
Regional, International Study of Durvalumab in Combination with Gemcitabine Plus Cisplatin Versus Placebo in Combination with Gemcitabine Plus Cisplatin for Patients With First-Line Advanced Biliary Tract Cancers (TOPAZ-1)
2. SWOG-S1815 - A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers
3. UCI 18-104 - A Phase III, Open-Label, Randomized, Active-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of INCB054828 versus Gemcitabine Plus Cisplatin Chemotherapy in First-Line Treatment of Participants with Unresectable or Metastatic Cholangiocarcinoma with FGFR2 Rearrangement
An Approach to Personalised Medicine in Advanced BTC Today/Tomorrow
Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium
Thank You
Treatment Options for Advanced CholangiocarcinomaEpidemiologyGemcitabine/Cisplatin in 1L advanced Cholangiocarcinoma: ABC-02 TrialSlide Number 4Slide Number 5ABC-06: second–line mFOLFOX vs active symptom controlMolecular characterization of cholangiocarcinomaTargeted Therapy for Biliary Tract CancersSlide Number 9Targeting IDH1 population (ClarIDHy)ClarIDHy Trial: Overall Survival�Slide Number 12FIGHT-202: a phase 2 study of pemigatinib in patients with previously treated locally advanced or metastatic CCAFIGHT-202: Response and Survival Cohort ATargeted Therapy in Molecularly-Altered Advanced Cholangiocarcinoma Other promising targets not to overlook in BTCLocoregional Treatment in Advanced IHCLocoregional Treatment in Advanced IHCClinical Trial Currently Enrolling at UC Irvine:An Approach to Personalised Medicine in Advanced BTC Today/TomorrowThank You��[email protected]