Exploring the Clinical Use of Molecular Profiling of Intrahepatic Cholangiocarcinoma in a Comprehensive Multidisciplinary Clinic.
Journal
Journal of the American College of Surgeons
ISSN: 1879-1190
Titre abrégé: J Am Coll Surg
Pays: United States
ID NLM: 9431305
Informations de publication
Date de publication:
01 Apr 2024
01 Apr 2024
Historique:
medline:
18
3
2024
pubmed:
8
1
2024
entrez:
8
1
2024
Statut:
ppublish
Résumé
Molecular profiling of intrahepatic cholangiocarcinoma (ICC) can detect actionable molecular alterations and guide targeted therapies. We explore the clinical use of molecular profiling of ICC in our comprehensive multidisciplinary clinic. Patients with a tissue diagnosis of ICC seen between 2019 and 2023 were identified. A retrospective review was performed to identify their molecular profiles and targeted therapy. The association between the detection of actionable molecular alterations and overall survival (OS) from the first clinic visit date was studied. Patients with an OS of less than 2 months were excluded. Among 194 patients with ICC, 125 had molecular profiling. Actionable molecular alterations were detected in 56 (45%) patients, including microsatellite instability (n = 3), high tumor mutational burden (>10 muts/mb; n = 5), isocitrate dehydrogenase 1 and 2 mutations (n = 22 and 6, respectively), BRAF V600E mutations (n = 2), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha mutations (n = 7), breast cancer 1 and breast cancer 2 mutations (n = 5), mesenchymal epithelial transition amplification (n = 2), fibroblast growth factor receptor 2 and 3 fusions (n = 13), erb-b2 receptor tyrosine kinase 2 overexpression (n = 6), and receptor tyrosine kinase 1 fusion (n = 1). Twenty-one patients received targeted therapies during their treatment course. Survival analysis revealed that for 120 patients with molecular profiling, the detection of an actionable molecular alteration was associated with improved mean OS (34.1 vs 23.6 months, p = 0.008). Among 70 patients with nonmetastatic ICC, the detection of an actionable molecular alteration was associated with improved mean OS (32.1 vs 27.5 months, p = 0.02). Actionable molecular alterations were frequently observed in patients with ICC. Detection of actionable alterations was associated with improved OS. The role of targeted therapy needs further exploration in prospective multicenter studies.
Sections du résumé
BACKGROUND
BACKGROUND
Molecular profiling of intrahepatic cholangiocarcinoma (ICC) can detect actionable molecular alterations and guide targeted therapies. We explore the clinical use of molecular profiling of ICC in our comprehensive multidisciplinary clinic.
STUDY DESIGN
METHODS
Patients with a tissue diagnosis of ICC seen between 2019 and 2023 were identified. A retrospective review was performed to identify their molecular profiles and targeted therapy. The association between the detection of actionable molecular alterations and overall survival (OS) from the first clinic visit date was studied. Patients with an OS of less than 2 months were excluded.
RESULTS
RESULTS
Among 194 patients with ICC, 125 had molecular profiling. Actionable molecular alterations were detected in 56 (45%) patients, including microsatellite instability (n = 3), high tumor mutational burden (>10 muts/mb; n = 5), isocitrate dehydrogenase 1 and 2 mutations (n = 22 and 6, respectively), BRAF V600E mutations (n = 2), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha mutations (n = 7), breast cancer 1 and breast cancer 2 mutations (n = 5), mesenchymal epithelial transition amplification (n = 2), fibroblast growth factor receptor 2 and 3 fusions (n = 13), erb-b2 receptor tyrosine kinase 2 overexpression (n = 6), and receptor tyrosine kinase 1 fusion (n = 1). Twenty-one patients received targeted therapies during their treatment course. Survival analysis revealed that for 120 patients with molecular profiling, the detection of an actionable molecular alteration was associated with improved mean OS (34.1 vs 23.6 months, p = 0.008). Among 70 patients with nonmetastatic ICC, the detection of an actionable molecular alteration was associated with improved mean OS (32.1 vs 27.5 months, p = 0.02).
CONCLUSIONS
CONCLUSIONS
Actionable molecular alterations were frequently observed in patients with ICC. Detection of actionable alterations was associated with improved OS. The role of targeted therapy needs further exploration in prospective multicenter studies.
Identifiants
pubmed: 38189646
doi: 10.1097/XCS.0000000000000948
pii: 00019464-202404000-00028
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
532-540Informations de copyright
Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.
Références
Izquierdo-Sanchez L, Lamarca A, La Casta A, et al. Cholangiocarcinoma landscape in Europe: diagnostic, prognostic and therapeutic insights from the ENSCCA Registry. J Hepatol. 2022;76:1109–1121.
Tella SH, Kommalapati A, Borad MJ, Mahipal A. Second-line therapies in advanced biliary tract cancers. Lancet Oncol. 2020;21:e29–e41.
Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–1281.
Do-Youn O, He Aiwu R, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evidence. 2022;1:EVIDoa2200015.
Kelley RK, Ueno M, Yoo C, et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;401:1853–1865.
Jusakul A, Cutcutache I, Yong CH, et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov. 2017;7:1116–1135.
Bekaii-Saab TS, Bridgewater J, Normanno N. Practical considerations in screening for genetic alterations in cholangiocarcinoma. Ann Oncol. 2021;32:1111–1126.
Malenica I, Donadon M, Lleo A. Molecular and immunological characterization of biliary tract cancers: a paradigm shift towards a personalized medicine. Cancers. 2020;12:2190.
Putra J, de Abreu FB, Peterson JD, et al. Molecular profiling of intrahepatic and extrahepatic cholangiocarcinoma using next generation sequencing. Exp Mol Pathol. 2015;99:240–244.
Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21:671–684.
Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:796–807.
Pishvaian MJ, Bender RJ, Halverson D, et al. Molecular profiling of patients with pancreatic cancer: initial results from the know your tumor initiative. Clin Cancer Res. 2018;24:5018–5027.
Pishvaian MJ, Blais EM, Brody JR, et al. Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial. Lancet Oncol. 2020;21:508–518.
El-Deiry WS, Vijayvergia N, Xiu J, et al. Molecular profiling of 6,892 colorectal cancer samples suggests different possible treatment options specific to metastatic sites. Cancer Biol Ther. 2015;16:1726–1737.
Raparia K, Villa C, DeCamp MM, et al. Molecular profiling in non–small cell lung cancer: a step toward personalized medicine. Arch Pathol Lab Med. 2013;137:481–491.
Manne A, Woods E, Tsung A, Mittra A. Biliary tract cancers: treatment updates and future directions in the era of precision medicine and immuno-oncology. Front Oncol. 2021;11:768009.
Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383:2168–2179.
Benson AB, D’Angelica MI, Abrams T, et al. NCCN Guidelines® insights: biliary tract cancers, version 22023: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2023;21:694–704.
Makawita S, Abou-Alfa G K, Roychowdhury S, et al. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Future Oncol. 2020;16:2375–2384.
Goyal L, Meric-Bernstam F, Hollebecque A, et al. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N Engl J Med. 2023;388:228–239.
Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion–positive cancers in adults and children. N Engl J Med. 2018;378:731–739.
Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials. Lancet Oncol. 2020;21:271–282.
Subbiah V, Lassen U, Élez E, et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020;21:1234–1243.
Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair–deficient cancer: results from the phase II KEYNOTE-158 study. JCO. 2020;38:1–10.
Jia AY, Popovic A, Mohan AA, et al. Development, practice patterns, and early clinical outcomes of a multidisciplinary liver cancer clinic. Cancer Control. 2021;28:10732748211009945.
Zhao B, Cheng Q, Cao H, et al. Dynamic change of serum CA19–9 levels in benign and malignant patients with obstructive jaundice after biliary drainage and new correction formulas. BMC Cancer. 2021;21:517.
Zhang XF, Beal EW, Bagante F, et al. Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent. Br J Surg. 2018;105:848–856.
Tsilimigras DI, Sahara K, Wu L, et al. Very early recurrence after liver resection for intrahepatic cholangiocarcinoma: considering alternative treatment approaches. JAMA Surg. 2020;155:823–831.
Hirsch FR, Suda K, Wiens J, Bunn PA. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016;388:1012–1024.
Manzi J, Hoff CO, Ferreira R, et al. Targeted Therapies in Colorectal Cancer: Recent Advances in Biomarkers, Landmark Trials, and Future Perspectives. Cancers. 2023;15:10–12.
Xie YH, Chen YX, Fang JY. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 2020;5:22.
Kendre G, Murugesan K, Brummer T, et al. Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma. J Hepatol. 2023;78:614–626.
Israel MA, Danziger N, McGregor KA, et al. Comparative genomic analysis of intrahepatic cholangiocarcinoma: biopsy type, ancestry, and testing patterns. Oncologist. 2021;26:787–796.
Huang P, Zhou Y, Chen Y. Significant response to camrelizumab plus targeted drugs in recurrent intrahepatic cholangiocarcinoma: a case report and literature review. J Gastrointest Cancer. 2022;53:817–824.
Golan T, Raitses‐Gurevich M, Kelley RK, et al. Overall survival and clinical characteristics of BRCA‐associated cholangiocarcinoma: a multicenter retrospective study. Oncologist. 2017;22:804–810.
Verlingue L, Malka D, Allorant A, et al. Precision medicine for patients with advanced biliary tract cancers: an effective strategy within the prospective MOSCATO-01 trial. Eur J Cancer. 2017;87:122–130.