&lt;p&gt;Completely resolved advanced biliary tract cancer after treatment by pembrolizumab: a report of two cases&lt;/p&gt;

Alshari, Osama; Dawaymeh, Tamara A; Tashtush, Nour A.; Aleshawi, Abdelwahab; Manasra, Abdel Rahman Al; Obeidat, Khaled

doi:10.2147/ott.s197559

Cited by 20 publications

(13 citation statements)

References 25 publications

(28 reference statements)

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“…Of note, none of the patients across the two studies were MSI [92]. Interestingly, two cases of complete disease resolution were reported after pembrolizumab alone in second-line treatment [94].…”

Section: Ici Monotherapymentioning

confidence: 94%

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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Section: Ici Monotherapymentioning

confidence: 94%

Immune Therapy for Liver Cancers

Hilmi

Vienot

Rousseau

et al. 2019

Cancers

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“…53,54 These findings are supported by case reports, which also detail profound and prolonged responses to ICIs in patients with CCA and known MSI or MMR deficiency, high TMB, or high rates of insertion or deletion mutations, which can result in neoantigens. [77][78][79][80][81] However, in microsatellite-stable, non-MMR deficient CCA, the ORR to ICI monotherapy appears much lower, though data are mixed. To date, KEYNOTE-158 (NCT02628067) is the largest study of ICI monotherapy with pembrolizumab; it includes patients with advanced biliary cancers without known MMR deficiency, after progression on or intolerance to at least 1 line of standard therapy.…”

Section: Tumour Immune Microenvironmentmentioning

confidence: 99%

Systemic therapies for intrahepatic cholangiocarcinoma

Kelley

Bridgewater

Gores

et al. 2020

Journal of Hepatology

276

206

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Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary neoplasm whose incidence is increasing. Largely neglected for decades as a rare malignancy and frequently misdiagnosed as carcinoma of unknown primary, considerable clinical and investigative attention has recently been focused on iCCA worldwide. The established standard of care includes first-line (gemcitabine and cisplatin), second-line (FOLFOX) and adjuvant (capecitabine) systemic chemotherapy. Compared to hepatocellular carcinoma, iCCA is genetically distinct with several targetable genetic aberrations identified to date. Indeed, FGFR2 and NTRK fusions, and IDH1 and BRAF targetable mutations have been comprehensively characterised and clinical data is emerging on targeting these oncogenic drivers pharmacologically. Also, the role of immunotherapy has been examined and is an area of intense investigation. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research.

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“…( 54 ) Although current studies on immunotherapy in CCA are limited, pembrolizumab, which is an anti‐PD‐1 antibody, showed promising results in patients with advanced CCA and is approved for microsatellite instability/mismatch unresectable or metastatic solid cancers, including hepatobiliary cancers. ( 61,62 ) A study using laser capture microdissection with 78 iCCA cases has identified four immune subtypes in the tumor microenvironment. ( 63 ) These subtypes had different populations and profiles of infiltrating cells as well as different gene expression profiles in inflammatory and immune checkpoint pathways, indicating that effects of immunotherapy such as PD‐1 antibodies may be limited to a certain percentage of patients with CCA.…”

Section: Functional Roles Of the Cca Microenvironmentmentioning

confidence: 99%