Ann Hepatobiliary Pancreat Surg.  2023 May;27(2):123-130. 10.14701/ahbps.22-110.

Intrahepatic cholangiocarcinoma: Evolving role of neoadjuvant and targeted therapy

Affiliations
  • 1Division of Hepato-Pancreato-Biliary & Abdominal Transplant Surgery, Tulane Abdominal Transplant Institute, Tulane University School of Medicine, New Orleans, LA, United States

Abstract

Intrahepatic cholangiocarcinoma is an aggressive, often fatal, malignancy that arises from the bile ducts. As it often presents with metastatic disease, surgery has limited utility. However, in some cases, neoadjuvant chemotherapy has provided the necessary reduction in tumor burden to allow for adequate resection. Consequently, new advances in neoadjuvant chemoradiation and targeted therapy are of interest with numerous case reports and small series published routinely; it is challenging to present a large case series or study given the overall rare frequency with which this malignancy is seen. Herein, we aim to summarize the newest advances in both neoadjuvant chemotherapy and targeted immunotherapy.

Keyword

Cholangiocarcinoma; Neoadjuvant treatment; Targeted; Immunotherapy

Reference

1. Rizzo A, Brandi G. 2021; Neoadjuvant therapy for cholangiocarcinoma: a comprehensive literature review. Cancer Treat Res Commun. 27:100354. DOI: 10.1016/j.ctarc.2021.100354. PMID: 33756174.
Article
2. Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. 2017; New horizons for precision medicine in biliary tract cancers. Cancer Discov. 7:943–962. DOI: 10.1158/2159-8290.CD-17-0245. PMID: 28818953. PMCID: PMC5586506.
Article
3. Raufi AG, Manji GA, Chabot JA, Bates SE. 2019; Neoadjuvant treatment for pancreatic cancer. Semin Oncol. 46:19–27. DOI: 10.1053/j.seminoncol.2018.12.002. PMID: 30630600.
Article
4. Jung JH, Lee HJ, Lee HS, Jo JH, Cho IR, Chung MJ, et al. 2017; Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma. World J Gastroenterol. 23:3301–3308. DOI: 10.3748/wjg.v23.i18.3301. PMID: 28566890. PMCID: PMC5434436.
Article
5. Sumiyoshi T, Shima Y, Okabayashi T, Negoro Y, Shimada Y, Iwata J, et al. 2018; Chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. World J Surg. 42:2910–2918. DOI: 10.1007/s00268-018-4558-1. PMID: 29511872.
Article
6. Kato A, Shimizu H, Ohtsuka M, Yoshidome H, Yoshitomi H, Furukawa K, et al. 2013; Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study. Ann Surg Oncol. 20:318–324. DOI: 10.1245/s10434-012-2312-8. PMID: 23149849.
Article
7. Stein A, Arnold D, Bridgewater J, Goldstein D, Jensen LH, Klümpen HJ, et al. 2015; Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial. BMC Cancer. 15:564. DOI: 10.1186/s12885-015-1498-0. PMID: 26228433. PMCID: PMC4520064.
Article
8. Nakachi K, Konishi M, Ikeda M, Mizusawa J, Eba J, Okusaka T, et al. 2018; A randomized Phase III trial of adjuvant S-1 therapy vs. observation alone in resected biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1202, ASCOT). Jpn J Clin Oncol. 48:392–395. DOI: 10.1093/jjco/hyy004. PMID: 29462482.
Article
9. Ibrahim SM, Mulcahy MF, Lewandowski RJ, Sato KT, Ryu RK, Masterson EJ, et al. 2008; Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer. 113:2119–2128. DOI: 10.1002/cncr.23818. PMID: 18759346.
Article
10. Mouli S, Memon K, Baker T, Benson AB 3rd, Mulcahy MF, Gupta R, et al. 2013; Yttrium-90 radioembolization for intrahepatic cholangiocarcinoma: safety, response, and survival analysis. J Vasc Interv Radiol. 24:1227–1234. DOI: 10.1016/j.jvir.2013.02.031. PMID: 23602420. PMCID: PMC3800023.
Article
11. Saxena A, Bester L, Chua TC, Chu FC, Morris DL. 2010; Yttrium-90 radiotherapy for unresectable intrahepatic cholangiocarcinoma: a preliminary assessment of this novel treatment option. Ann Surg Oncol. 17:484–491. DOI: 10.1245/s10434-009-0777-x. PMID: 19876691.
Article
12. Edeline J, Touchefeu Y, Guiu B, Farge O, Tougeron D, Baumgaertner I, et al. 2020; Radioembolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 6:51–59. DOI: 10.1001/jamaoncol.2019.3702. PMID: 31670746. PMCID: PMC6824230.
Article
13. Riby D, Mazzotta AD, Bergeat D, Verdure L, Sulpice L, Bourien H, et al. 2020; Downstaging with radioembolization or chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. Ann Surg Oncol. 27:3729–3737. DOI: 10.1245/s10434-020-08486-7. PMID: 32472411.
Article
14. Kato A, Shimizu H, Ohtsuka M, Yoshitomi H, Furukawa K, Takayashiki T, et al. 2015; Downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer patients treated with gemcitabine plus cisplatin combination therapy followed by radical surgery. Ann Surg Oncol. 22 Suppl 3:S1093–S1099. DOI: 10.1245/s10434-015-4768-9. PMID: 26240009.
Article
15. Rayar M, Sulpice L, Edeline J, Garin E, Levi Sandri GB, Meunier B, et al. 2015; Intra-arterial yttrium-90 radioembolization combined with systemic chemotherapy is a promising method for downstaging unresectable huge intrahepatic cholangiocarcinoma to surgical treatment. Ann Surg Oncol. 22:3102–3108. DOI: 10.1245/s10434-014-4365-3. PMID: 25623598.
Article
16. Le Roy B, Gelli M, Pittau G, Allard MA, Pereira B, Serji B, et al. 2018; Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. Br J Surg. 105:839–847. DOI: 10.1002/bjs.10641. PMID: 28858392.
Article
17. Kamarajah S, Giovinazzo F, Roberts KJ, Punia P, Sutcliffe RP, Marudanayagam R, et al. 2020; The role of down staging treatment in the management of locally advanced intrahepatic cholangiocarcinoma: review of literature and pooled analysis. Ann Hepatobiliary Pancreat Surg. 24:6–16. DOI: 10.14701/ahbps.2020.24.1.6. PMID: 32181423. PMCID: PMC7061034.
Article
18. Lunsford KE, Javle M, Heyne K, Shroff RT, Abdel-Wahab R, Gupta N, et al. 2018; Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. Lancet Gastroenterol Hepatol. 3:337–348. Erratum in: Lancet Gastroenterol Hepatol 2018;3:e3. DOI: 10.1016/S2468-1253(18)30045-1. PMID: 29548617.
Article
19. Moris D, Rahnemai-Azar AA, Zhang X, Ntanasis-Stathopoulos I, Tsilimigras DI, Chakedis J, et al. 2017; Program death-1 immune checkpoint and tumor microenvironment in malignant liver tumors. Surg Oncol. 26:423–430. DOI: 10.1016/j.suronc.2017.08.005. PMID: 29113661.
Article
20. Ju JY, Dibbern ME, Mahadevan MS, Fan J, Kunk PR, Stelow EB. 2020; Mismatch repair protein deficiency/microsatellite instability is rare in cholangiocarcinomas and associated with distinctive morphologies. Am J Clin Pathol. 153:598–604. DOI: 10.1093/ajcp/aqz199. PMID: 31844887.
Article
21. Gou M, Zhang Y, Liu T, Si H, Wang Z, Yan H, et al. 2021; PD-1 inhibitors could improve the efficacy of chemotherapy as first-line treatment in biliary tract cancers: a propensity score matching based analysis. Front Oncol. 11:648068. DOI: 10.3389/fonc.2021.648068. PMID: 34221968. PMCID: PMC8248534.
Article
22. Zhang Z, Zhang W, Wang H, Hu B, Wang Z, Lu S. 2021; Successful treatment of advanced intrahepatic cholangiocarcinoma with a high tumor mutational burden and PD-L1 expression by PD-1 blockade combined with tyrosine kinase inhibitors: a case report. Front Immunol. 12:744571. DOI: 10.3389/fimmu.2021.744571. PMID: 34603331. PMCID: PMC8484748.
Article
23. Rizzo A, Ricci AD, Brandi G. 2021; Durvalumab: an investigational anti-PD-L1 antibody for the treatment of biliary tract cancer. Expert Opin Investig Drugs. 30:343–350. DOI: 10.1080/13543784.2021.1897102. PMID: 33645367.
Article
24. Borger DR, Tanabe KK, Fan KC, Lopez HU, Fantin VR, Straley KS, et al. 2012; Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist. 17:72–79. DOI: 10.1634/theoncologist.2011-0386. PMID: 22180306. PMCID: PMC3267826.
Article
25. Boscoe AN, Rolland C, Kelley RK. 2019; Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: a systematic literature review. J Gastrointest Oncol. 10:751–765. DOI: 10.21037/jgo.2019.03.10. PMID: 31392056. PMCID: PMC6657309.
Article
26. Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, et al. 2020; Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 21:796–807. Erratum in: Lancet Oncol 2020;21:e462. DOI: 10.1016/S1470-2045(20)30157-1. PMID: 32416072.
Article
27. Graham RP, Barr Fritcher EG, Pestova E, Schulz J, Sitailo LA, Vasmatzis G, et al. 2014; Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol. 45:1630–1638. DOI: 10.1016/j.humpath.2014.03.014. PMID: 24837095.
Article
28. Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, et al. 2020; Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 21:671–684. DOI: 10.1016/S1470-2045(20)30109-1. PMID: 32203698.
Article
29. Javle M, Lowery M, Shroff RT, Weiss KH, Springfeld C, Borad MJ, et al. 2018; Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 36:276–282. DOI: 10.1200/JCO.2017.75.5009. PMID: 29182496. PMCID: PMC6075847.
Article
30. Ikeda M, Ioka T, Fukutomi A, Morizane C, Kasuga A, Takahashi H, et al. 2018; Efficacy and safety of trametinib in Japanese patients with advanced biliary tract cancers refractory to gemcitabine. Cancer Sci. 109:215–224. DOI: 10.1111/cas.13438. PMID: 29121415. PMCID: PMC5765304.
Article
31. Bekaii-Saab T, Phelps MA, Li X, Saji M, Goff L, Kauh JS, et al. 2011; Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol. 29:2357–2363. DOI: 10.1200/JCO.2010.33.9473. PMID: 21519026. PMCID: PMC3107751.
Article
32. Subbiah V, Lassen U, Élez E, Italiano A, Curigliano G, Javle M, et al. 2020; Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 21:1234–1243. DOI: 10.1016/S1470-2045(20)30321-1. PMID: 32818466.
Article
33. Lavingia V, Fakih M. 2016; Impressive response to dual BRAF and MEK inhibition in patients with BRAF mutant intrahepatic cholangiocarcinoma-2 case reports and a brief review. J Gastrointest Oncol. 7:E98–E102. DOI: 10.21037/jgo.2016.09.13. PMID: 28078132. PMCID: PMC5177579.
Article
34. Churi CR, Shroff R, Wang Y, Rashid A, Kang HC, Weatherly J, et al. 2014; Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications. PLoS One. 9:e115383. DOI: 10.1371/journal.pone.0115383. PMID: 25536104. PMCID: PMC4275227.
Article
35. Galdy S, Lamarca A, McNamara MG, Hubner RA, Cella CA, Fazio N, et al. 2017; HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target? Cancer Metastasis Rev. 36:141–157. DOI: 10.1007/s10555-016-9645-x. PMID: 27981460. PMCID: PMC5385197.
Article
36. Amin NEL, Hansen TF, Fernebro E, Ploen J, Eberhard J, Lindebjerg J, et al. 2021; Randomized Phase II trial of combination chemotherapy with panitumumab or bevacizumab for patients with inoperable biliary tract cancer without KRAS exon 2 mutations. Int J Cancer. 149:119–126. DOI: 10.1002/ijc.33509. PMID: 33561312.
Article
37. Golan T, Raitses-Gurevich M, Kelley RK, Bocobo AG, Borgida A, Shroff RT, et al. 2017; Overall survival and clinical characteristics of BRCA-associated cholangiocarcinoma: a multicenter retrospective study. Oncologist. 22:804–810. DOI: 10.1634/theoncologist.2016-0415. PMID: 28487467. PMCID: PMC5507643.
Article
38. Fouassier L, Marzioni M, Afonso MB, Dooley S, Gaston K, Giannelli G, et al. 2019; Signalling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance. Liver Int. 39 Suppl 1:43–62. DOI: 10.1111/liv.14102. PMID: 30903728.
Article
39. Isomoto H. 2009; Epigenetic alterations in cholangiocarcinoma-sustained IL-6/STAT3 signaling in cholangio- carcinoma due to SOCS3 epigenetic silencing. Digestion. 79 Suppl 1:2–8. DOI: 10.1159/000167859. PMID: 19153483.
Article
40. Wang W, Zhong W, Yuan J, Yan C, Hu S, Tong Y, et al. 2015; Involvement of Wnt/β-catenin signaling in the mesenchymal stem cells promote metastatic growth and chemoresistance of cholangiocarcinoma. Oncotarget. 6:42276–42289. DOI: 10.18632/oncotarget.5514. PMID: 26474277. PMCID: PMC4747224.
Article
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