FIGHT-202: A phase II study of pemigatinib in patients (pts) with previously treated locally advanced or metastatic cholangiocarcinoma (CCA)

Vogel, Arndt; Sahai, Vaibhav; Hollebecque, Antoine; Vaccaro, Gina M.; Melisi, Davide; Al‐Rajabi, Raed; Paulson, Andrew Scott; Borad, Mitesh J.; Gallinson, David; Murphy, Adrian; Oh, Do‐Youn; Dotan, Efrat; Catenacci, Daniel V.T.; Cutsem, Éric Van; Lihou, Christine; Zhen, Huiling; Féliz, Luis; Abou‐Alfa, Ghassan K.

doi:10.1093/annonc/mdz394.031

Cited by 58 publications

(52 citation statements)

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“…78 In such a context, infigratinib, derazantinib and pemigatinib showed overall response rates of 19%, 21% and 36%, and disease control rates of 83%, 83% and 82%, respectively, even though progression-free survival remains around 6 months, mainly due to primary and secondary resistance. [79][80][81] These small molecules evaluated in phase II trials for advanced iCCA may possibly represent future alternative options in the adjuvant setting in light of premiminary data on their manageable toxicity.…”

Section: Key Pointmentioning

confidence: 99%

Liver resection and transplantation for intrahepatic cholangiocarcinoma

Mazzaferro

Gorgen

Roayaie

et al. 2020

Journal of Hepatology

254

182

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The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing worldwide. Although several advances have been made in the past decades to better understand this complex malignancy and to develop new treatment strategies, the prognosis of iCCA remains dismal. Liver resection (LR) is the mainstay of treatment but only a minority of patients are amenable to surgery. In most cases, patients with iCCA will require a major hepatectomy for complete resection of the tumour. This may be contraindicated or increase the surgical burden in patients with chronic liver disease and small remnant liver volume. Lymphadenectomy with a minimal harvest of 6 lymph nodes is considered adequate, as microscopic nodal metastases have been shown in more than 40% of patients. Current 5-year overall survival following LR is in the range of 25%-40%. For locally advanced disease not amenable to upfront LR, neoadjuvant locoregional therapies may be used with the aim of converting these patients to resectability or even to transplantation in well-selected cases. Recent studies have shown that liver transplantation (LT) might be a treatment option for patients with unresectable very-early iCCA (i.e. < − 2 cm), with survival outcomes comparable to those of hepatocellular carcinoma. In patients with unresectable, advanced tumours, confined to the liver who achieve sustained response to neoadjuvant treatment, LT may be considered an option within prospective protocols. The role of adjuvant therapies in iCCA is still under debate. Herein, we review the recent advances in the surgical treatment of iCCA and examine its correlation with locoregional therapies, adjuvant and neo-adjuvant strategies.

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Section: Key Pointmentioning

confidence: 99%

Liver resection and transplantation for intrahepatic cholangiocarcinoma

Mazzaferro

Gorgen

Roayaie

et al. 2020

Journal of Hepatology

254

182

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“…IDH and FGFR alterations represent the two main "modern" therapeutic targets in BTCs and are the most advanced in their clinical development. [71,72]. receptor 2 (FGFR2) gene fusions were each described in 10-20% of iCCA [70].…”

Section: Molecular Alterationsmentioning

confidence: 99%

“…IDH and FGFR alterations represent the two main "modern" therapeutic targets in BTCs and are the most advanced in their clinical development. [71,72].…”

Section: Molecular Alterationsmentioning

confidence: 99%

“…The identification of BTC subtypes with specific genomic alterations, some of which may be druggable, led to the hypothesis that treatment may be personalized for each patient based on molecular profiling of tumors [65]. However, although the first success emerged with IDH and FGFR targeting [71,72], there is currently no treatment development in selected subpopulations associated with an immune signature.…”

Section: Subgroups Sensitive To Immune Therapiesmentioning

confidence: 99%

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Immune Therapy for Liver Cancers

Hilmi

Vienot

Rousseau

et al. 2019

Cancers

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Hepatocellular carcinoma (HCC) and biliary tract cancers (BTC) display a poor prognosis with 5-year overall survival rates around 15%, all stages taken together. These primary liver malignancies are often diagnosed at advanced stages where therapeutic options are limited. Recently, immune therapy has opened new opportunities in oncology. Based on their high programmed death-ligand 1 expression and tumor-infiltrating lymphocytes, HCC and BTC are theoretically good candidates for immune checkpoint blockade. However, clinical activity of single agent immunotherapy appears limited to a subset of patients, which is still ill-defined, and combinations are under investigation. In this review, we provide an overview of (i) the biological rationale for immunotherapies in HCC and BTC, (ii) the current state of their clinical development, and (iii) the predictive value of immune signatures for both clinical outcome and response to these therapies.

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“…A recent phase III study with ivosidenib, an inhibitor of the mutant IDH1 protein, has shown improved progression-free survival in CCA patients with mutated IDH1 [158]. The results of a phase II trial for pemigatinib, an FGFR inhibitor, in CCA patients harboring FGFR2 fusions or rearrangements are also promising [159].…”

Section: Anticancer Drugsmentioning

confidence: 99%

Role of Genetic Variations in the Hepatic Handling of Drugs

Marin

Serrano

Monte

et al. 2020

IJMS

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The liver plays a pivotal role in drug handling due to its contribution to the processes of detoxification (phases 0 to 3). In addition, the liver is also an essential organ for the mechanism of action of many families of drugs, such as cholesterol-lowering, antidiabetic, antiviral, anticoagulant, and anticancer agents. Accordingly, the presence of genetic variants affecting a high number of genes expressed in hepatocytes has a critical clinical impact. The present review is not an exhaustive list but a general overview of the most relevant variants of genes involved in detoxification phases. The available information highlights the importance of defining the genomic profile responsible for the hepatic handling of drugs in many ways, such as (i) impaired uptake, (ii) enhanced export, (iii) altered metabolism due to decreased activation of prodrugs or enhanced inactivation of active compounds, and (iv) altered molecular targets located in the liver due to genetic changes or activation/downregulation of alternative/compensatory pathways. In conclusion, the advance in this field of modern pharmacology, which allows one to predict the outcome of the treatments and to develop more effective and selective agents able to overcome the lack of effect associated with the existence of some genetic variants, is required to step forward toward a more personalized medicine.

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FIGHT-202: A phase II study of pemigatinib in patients (pts) with previously treated locally advanced or metastatic cholangiocarcinoma (CCA)

Cited by 58 publications

References 0 publications

Liver resection and transplantation for intrahepatic cholangiocarcinoma

Liver resection and transplantation for intrahepatic cholangiocarcinoma

Immune Therapy for Liver Cancers

Role of Genetic Variations in the Hepatic Handling of Drugs

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