O-4 NTRK gene fusions in bilio-pancreatic cancers

Demols, A.; Pérez-Casanova, Luis; Rocq, Laureen; Charry, Manon; Nève, Nancy De; Verrellen, Audrey; Ramadhan, Ali A; Campenhout, Claude Van; Clercq, Sarah De; Maris, Calliope; Closset, Jean; Lucidi, Valério; Salmon, Isabelle; D’Haene, Nicky

doi:10.1016/j.annonc.2020.04.057

Cited by 6 publications

(4 citation statements)

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“… 74 As a pioneer of broad‐spectrum anticancer drugs, NTRK inhibitors may play a role in a small proportion of patients with BTC (0.67%). 75 In a previous study, 54 patients with advanced or metastatic NTRK fusion‐positive solid tumors (one patient with CCA) treated with entrectinib achieved an ORR of 57%. 76 Larotrectinib (another highly selective NTRK inhibitor) also showed excellent antitumor activity in patients with NTRK fusion‐positive tumors, with an ORR of 93% (14 of 15 patients).…”

Section: Targeted Therapy In Ccamentioning

confidence: 95%

Emerging treatment evolutions and integrated molecular characteristics of biliary tract cancers

et al. 2021

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Biliary tract cancers (BTCs) consist of a group of highly heterogeneous malignancies that are characterized by genomic differences among tumors from different anatomic sites. The current treatment for BTC includes surgery, chemotherapy, target therapy, and immunotherapy. Although surgery remains the primary option for localized disease, representing the only potential curative treatment, a high risk of recurrence cannot be neglected. Chemotherapy has been considered the standard of care for both advanced and metastatic disease and in adjuvant settings. However, drug resistance is a major obstacle associated with chemotherapy. The development of genetic testing technologies, including next-generation sequencing, has opened the door for the identification of drug targets and candidate molecules. A series of preclinical studies has demonstrated the role of gene mutations, abnormal signaling pathways, and immunosuppression in the pathogenesis of BTC, laying the foundation for the application of targeted therapy and immunotherapy. A variety of molecularly targeted agents, including pemigatinib, have shown promising survival benefits in patients with advanced disease. The rapidly evolving role of multimodal therapy represents the subject of this review.

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Section: Targeted Therapy In Ccamentioning

confidence: 95%

Emerging treatment evolutions and integrated molecular characteristics of biliary tract cancers

et al. 2021

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“…An ORR of 75% (95% CI 61–85) was seen, with 55% of patients remaining progression-free at 1 year of follow-up [ 156 ]. These encouraging results were tempered by a more recent sequencing study of 149 BTCs, which identified only one NTRK fusion (a pCCA), for an overall frequency of 0.67% [ 36 ]. Two basket trials of NTRK TKIs in patients with previously treated BTC are ongoing (NCT02568267 and NCT02576431).…”

Section: Potentially Actionable Molecular Aberrations In Perihilar Ch...mentioning

confidence: 99%

“… Frequency of potentially actionable molecular aberrations in perihilar cholangiocarcinoma. Anatomical groupings of patients sampled to determine each frequency are beside/below the corresponding frequency [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Rates of co-occurrence of the described molecular aberrations within patients are unknown.…”

Section: Figurementioning

confidence: 99%

Targeted Therapies for Perihilar Cholangiocarcinoma

Gray

Lamarca

Edeline

et al. 2022

Cancers

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Perihilar cholangiocarcinoma (pCCA) is the anatomical sub-group of biliary tract cancer (BTC) arising between the second-order intrahepatic bile ducts and the cystic duct. Together with distal and intrahepatic cholangiocarcinoma (dCCA and iCCA; originating distal to, and proximal to this, respectively), gallbladder cancer (GBC) and ampulla of Vater carcinoma (AVC), these clinicopathologically and molecularly distinct entities comprise biliary tract cancer (BTC). Most pCCAs are unresectable at diagnosis, and for those with resectable disease, surgery is extensive, and recurrence is common. Therefore, the majority of patients with pCCA will require systemic treatment for advanced disease. The prognosis with cytotoxic chemotherapy remains poor, driving interest in therapies targeted to the molecular nature of a given patient’s cancer. In recent years, the search for efficacious targeted therapies has been fuelled both by whole-genome and epigenomic studies, looking to uncover the molecular landscape of CCA, and by specifically testing for aberrations where established therapies exist in other indications. This review aims to provide a focus on the current molecular characterisation of pCCA, targeted therapies applicable to pCCA, and future directions in applying personalised medicine to this difficult-to-treat malignancy.

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“…The role of TRK inhibitors was firstly explored by a pivotal trial evaluating the role of larotrectinib in 55 NTRK-positive solid tumors, including two previously treated eCCAs [94]; according to the results of the primary data cutoff, 13% of patients achieved complete response to larotrectinib and 62% a partial response. A recent study presented at ESMO World Congress on Gastrointestinal Cancer 2020 tried to determine the incidence of NTRK gene fusions in bilio-pancreatic malignancies, including pancreatic cancer and BTCs [95]. According to the results of this report, the presence of NTRK gene fusions was observed in only 0.67% of overall BTC malignancies.…”

Section: Other Targeted Agents In Clinical Developmentmentioning

confidence: 99%

Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures

Rizzo

Tavolari

Ricci

et al. 2020

Cancers

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Biliary tract cancers (BTCs) include a heterogenous group of aggressive malignancies with limited therapeutic options. According to their anatomical location, these hepatobiliary tumors are usually classified into intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer (GBC). Unfortunately, BTCs are often diagnosed when already metastatic, and although the advent of genomic sequencing has led to a deeper understanding of iCCA pathogenesis, very little data are currently available about the molecular landscape of eCCA. Moreover, despite novel systemic treatments emerging in BTC, the grim prognosis of eCCA patients has not changed in the past decade, and no targeted therapies have been approved so far. The aim of the current review is to provide an overview regarding molecular features and potential targeted therapies in eCCA, together with novel therapeutic approaches and future directions of translational and clinical research on this highly aggressive disease that poses many unanswered questions.

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O-4 NTRK gene fusions in bilio-pancreatic cancers

Cited by 6 publications

References 0 publications

Emerging treatment evolutions and integrated molecular characteristics of biliary tract cancers

Emerging treatment evolutions and integrated molecular characteristics of biliary tract cancers

Targeted Therapies for Perihilar Cholangiocarcinoma

Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures

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