Evolving Paradigms in the Systemic Treatment of Advanced Gallbladder Cancer: Updates in Year 2022
Abstract
Simple Summary
Abstract
1. Introduction
2. Risk Factors
3. Pathogenesis
4. Genomics
5. Treatment Options
5.1. Neoadjuvant Therapy for BTCs
5.2. Adjuvant Therapy
5.3. Systemic Therapy
Authors | Phase | Line of Treatment | Treatment | Median PFS (Months) | Median OS (Months) |
---|---|---|---|---|---|
Valle [61] ABC-02 study | 3 | 1 | GEMCIS vs. gemcitabine | 8 vs. 5 (p < 0.001) | 11.7 vs. 8.1 (p < 0.001) |
Shroff [56] | 2 | 1 | GEMCIS + nab-paclitaxel | 11.8 | 19.2 |
Williams [64] | 2 | 1 | Gemcitabine + carboplatin | 7.8 | 10.6 |
Kim [65] | 3 | 1 | CAPOX vs. GEMOX (non-inferior study) | 5.8 vs. 5.3 | 10.6 vs. 10.4 (p = 0.131) |
Lamarca [62] ABC-06 study | 3 | 2 | FOLFOX vs. symptom control | 4 vs. N/A | 6.2 vs. 5.3 (p = 0.031) |
Yoo [63] NIFTY study | 2 | 2 | 5-FU + liposomal irinotecan | 7.1 vs. 1.4 (p = 0.0019) | 8.6 vs. 5.5 (p = 0.035) |
6. Targeted Therapy
6.1. HER2/neu Pathway
6.2. FGFR Pathway
6.3. BRAF/MEK Pathway
6.4. PD-1 Pathway
7. Future Directions
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Han, D.; Yang, J.; Xu, F.; Huang, Q.; Bai, L.; Wei, Y.L.; Kaaya, R.E.; Wang, S.; Lyu, J. Prognostic factors in patients with gallbladder adenocarcinoma identified using competing-risks analysis: A study of cases in the SEER database. Medicine 2020, 99, e21322. [Google Scholar] [CrossRef]
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 2022, 72, 7–33. [Google Scholar] [CrossRef]
- Ellington, T.D.; Momin, B.; Wilson, R.J.; Henley, S.J.; Wu, M.; Ryerson, A.B. Incidence and Mortality of Cancers of the Biliary Tract, Gallbladder, and Liver by Sex, Age, Race/Ethnicity, and Stage at Diagnosis: United States, 2013 to 2017. Cancer Epidemiol. Biomarkers Prev. 2021, 30, 1607–1614. [Google Scholar] [CrossRef] [PubMed]
- Van Dyke, A.L.; Shiels, M.S.; Jones, G.S.; Pfeiffer, R.M.; Petrick, J.L.; Beebe-Dimmer, J.L.; Koshiol, J. Biliary tract cancer incidence and trends in the United States by demographic group, 1999–2013. Cancer 2019, 125, 1489–1498. [Google Scholar] [CrossRef] [PubMed]
- Hsing, A.W.; Gao, Y.T.; Han, T.Q.; Rashid, A.; Sakoda, L.C.; Wang, B.S.; Shen, M.C.; Zhang, B.H.; Niwa, S.; Chen, J.; et al. Gallstones and the risk of biliary tract cancer: A population-based study in China. Br. J. Cancer 2007, 97, 1577–1582. [Google Scholar] [CrossRef] [PubMed]
- Huang, D.; Joo, H.; Song, N.; Cho, S.; Kim, W.; Shin, A. Association between gallstones and the risk of biliary tract cancer: A systematic review and meta-analysis. Epidemiol. Health 2021, 43, e2021011. [Google Scholar] [CrossRef] [PubMed]
- Paraskevopoulos, J.A.; Dennison, A.R.; Ross, B.; Johnson, A.G. Primary carcinoma of the gallbladder: A 10-year experience. Ann. R. Coll. Surg. Engl. 1992, 74, 222–224. [Google Scholar]
- Lowenfels, A.B.; Lindstrom, C.G.; Conway, M.J.; Hastings, P.R. Gallstones and risk of gallbladder cancer. J. Natl. Cancer Inst. 1985, 75, 77–80. [Google Scholar]
- Muszynska, C.; Lundgren, L.; Lindell, G.; Andersson, R.; Nilsson, J.; Sandstrom, P.; Andersson, B. Predictors of incidental gallbladder cancer in patients undergoing cholecystectomy for benign gallbladder disease: Results from a population-based gallstone surgery registry. Surgery 2017, 162, 256–263. [Google Scholar] [CrossRef]
- Duffy, A.; Capanu, M.; Abou-Alfa, G.K.; Huitzil, D.; Jarnagin, W.; Fong, Y.; D’Angelica, M.; Dematteo, R.P.; Blumgart, L.H.; O’Reilly, E.M. Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC). J. Surg. Oncol. 2008, 98, 485–489. [Google Scholar] [CrossRef]
- Rahman, R.; Simoes, E.J.; Schmaltz, C.; Jackson, C.S.; Ibdah, J.A. Trend analysis and survival of primary gallbladder cancer in the United States: A 1973–2009 population-based study. Cancer Med. 2017, 6, 874–880. [Google Scholar] [CrossRef]
- Rawla, P.; Sunkara, T.; Thandra, K.C.; Barsouk, A. Epidemiology of gallbladder cancer. Clin. Exp. Hepatol. 2019, 5, 93–102. [Google Scholar] [CrossRef]
- Calle, E.E.; Rodriguez, C.; Walker-Thurmond, K.; Thun, M.J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 2003, 348, 1625–1638. [Google Scholar] [CrossRef]
- Engeland, A.; Tretli, S.; Austad, G.; Bjorge, T. Height and body mass index in relation to colorectal and gallbladder cancer in two million Norwegian men and women. Cancer Causes Control 2005, 16, 987–996. [Google Scholar] [CrossRef]
- Goldberg, M.S.; Theriault, G. Retrospective cohort study of workers of a synthetic textiles plant in Quebec: I. General mortality. Am. J. Ind. Med. 1994, 25, 889–907. [Google Scholar] [CrossRef]
- Onyije, F.M.; Hosseini, B.; Togawa, K.; Schuz, J.; Olsson, A. Cancer Incidence and Mortality among Petroleum Industry Workers and Residents Living in Oil Producing Communities: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2021, 18, 4343. [Google Scholar] [CrossRef]
- Malker, H.S.; McLaughlin, J.K.; Malker, B.K.; Stone, B.J.; Weiner, J.A.; Ericsson, J.L.; Blot, W.J. Biliary tract cancer and occupation in Sweden. Br. J. Ind. Med. 1986, 43, 257–262. [Google Scholar] [CrossRef]
- Dutta, U.; Garg, P.K.; Kumar, R.; Tandon, R.K. Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Am. J. Gastroenterol. 2000, 95, 784–787. [Google Scholar] [CrossRef]
- Nagaraja, V.; Eslick, G.D. Systematic review with meta-analysis: The relationship between chronic Salmonella typhi carrier status and gall-bladder cancer. Aliment. Pharmacol. Ther. 2014, 39, 745–750. [Google Scholar] [CrossRef]
- Win, A.K.; Lindor, N.M.; Young, J.P.; Macrae, F.A.; Young, G.P.; Williamson, E.; Parry, S.; Goldblatt, J.; Lipton, L.; Winship, I.; et al. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. J. Natl. Cancer Inst. 2012, 104, 1363–1372. [Google Scholar] [CrossRef]
- Espinoza, J.A.; Bizama, C.; Garcia, P.; Ferreccio, C.; Javle, M.; Miquel, J.F.; Koshiol, J.; Roa, J.C. The inflammatory inception of gallbladder cancer. Biochim. Biophys. Acta 2016, 1865, 245–254. [Google Scholar] [CrossRef]
- Barreto, S.G.; Dutt, A.; Chaudhary, A. A genetic model for gallbladder carcinogenesis and its dissemination. Ann. Oncol. 2014, 25, 1086–1097. [Google Scholar] [CrossRef]
- Roa, I.; de Aretxabala, X.; Araya, J.C.; Roa, J. Preneoplastic lesions in gallbladder cancer. J. Surg. Oncol. 2006, 93, 615–623. [Google Scholar] [CrossRef]
- Roa, I.; Araya, J.C.; Wistuba, I.; Villaseca, M.; de Aretxabala, X.; Busel, D.; Burgos, L. Epithelial lesions associated with gallbladder carcinoma. A methodical study of 32 cases. Rev. Med. Chil. 1993, 121, 21–29. [Google Scholar]
- Gonda, T.A.; Tu, S.; Wang, T.C. Chronic inflammation, the tumor microenvironment and carcinogenesis. Cell Cycle 2009, 8, 2005–2013. [Google Scholar] [CrossRef]
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
- Latorre, S.G.; Ivanovic-Zuvic, S.D.; Corsi, S.O.; Valdivia, C.G.; Margozzini, M.P.; Olea, O.R.; Chianale, B.J.; Miquel, P.J. Coverage of the gallbladder cancer prevention strategy in Chile: Results from the 2009–2010 National Health Survey. Rev. Med. Chil. 2015, 143, 158–167. [Google Scholar] [CrossRef][Green Version]
- Miquel, J.F.; Covarrubias, C.; Villaroel, L.; Mingrone, G.; Greco, A.V.; Puglielli, L.; Carvallo, P.; Marshall, G.; Del Pino, G.; Nervi, F. Genetic epidemiology of cholesterol cholelithiasis among Chilean Hispanics, Amerindians, and Maoris. Gastroenterology 1998, 115, 937–946. [Google Scholar] [CrossRef]
- Lorenzo Bermejo, J.; Boekstegers, F.; Gonzalez Silos, R.; Marcelain, K.; Baez Benavides, P.; Barahona Ponce, C.; Muller, B.; Ferreccio, C.; Koshiol, J.; Fischer, C.; et al. Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile. PLoS Genet. 2017, 13, e1006756. [Google Scholar] [CrossRef] [PubMed]
- Koshiol, J.; Van De Wyngard, V.; McGee, E.E.; Cook, P.; Pfeiffer, R.M.; Mardones, N.; Medina, K.; Olivo, V.; Pettit, K.; Jackson, S.S.; et al. The Chile Biliary Longitudinal Study: A Gallstone Cohort. Am. J. Epidemiol. 2021, 190, 196–206. [Google Scholar] [CrossRef] [PubMed]
- Jackson, S.S.; Van De Wyngard, V.; Pfeiffer, R.M.; Cook, P.; Hildesheim, A.; Pinto, L.A.; Jackson, S.H.; Choi, K.; Verdugo, R.A.; Cuevas, M.; et al. Inflammatory profiles in Chilean Mapuche and non-Mapuche women with gallstones at risk of developing gallbladder cancer. Sci. Rep. 2021, 11, 3686. [Google Scholar] [CrossRef]
- Elnemr, A.; Ohta, T.; Kayahara, M.; Kitagawa, H.; Yoshimoto, K.; Tani, T.; Shimizu, K.; Nishimura, G.; Terada, T.; Miwa, K. Anomalous pancreaticobiliary ductal junction without bile duct dilatation in gallbladder cancer. Hepatogastroenterology 2001, 48, 382–386. [Google Scholar]
- Hu, B.; Gong, B.; Zhou, D.Y. Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: An ERCP study. Gastrointest. Endosc. 2003, 57, 541–545. [Google Scholar] [CrossRef]
- Wang, H.P.; Wu, M.S.; Lin, C.C.; Chang, L.Y.; Kao, A.W.; Wang, H.H.; Lin, J.T. Pancreaticobiliary diseases associated with anomalous pancreaticobiliary ductal union. Gastrointest. Endosc. 1998, 48, 184–189. [Google Scholar] [CrossRef]
- Kimura, K.; Ohto, M.; Saisho, H.; Unozawa, T.; Tsuchiya, Y.; Morita, M.; Ebara, M.; Matsutani, S.; Okuda, K. Association of gallbladder carcinoma and anomalous pancreaticobiliary ductal union. Gastroenterology 1985, 89, 1258–1265. [Google Scholar] [CrossRef]
- Yoshida, T.; Shibata, K.; Matsumoto, T.; Sasaki, A.; Hirose, R.; Kitano, S. Carcinoma of the gallbladder associated with anomalous junction of the pancreaticobiliary duct in adults. J. Am. Coll. Surg. 1999, 189, 57–62. [Google Scholar] [CrossRef]
- Deng, Y.L.; Cheng, N.S.; Lin, Y.X.; Zhou, R.X.; Yang, C.; Jin, Y.W.; Xiong, X.Z. Relationship between pancreaticobiliary maljunction and gallbladder carcinoma: Meta-analysis. Hepatobiliary Pancreat. Dis. Int. 2011, 10, 570–580. [Google Scholar] [CrossRef]
- Lamarca, A.; Barriuso, J.; McNamara, M.G.; Valle, J.W. Molecular targeted therapies: Ready for “prime time” in biliary tract cancer. J. Hepatol. 2020, 73, 170–185. [Google Scholar] [CrossRef]
- Wu, Y.M.; Su, F.; Kalyana-Sundaram, S.; Khazanov, N.; Ateeq, B.; Cao, X.; Lonigro, R.J.; Vats, P.; Wang, R.; Lin, S.F.; et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013, 3, 636–647. [Google Scholar] [CrossRef]
- Sia, D.; Losic, B.; Moeini, A.; Cabellos, L.; Hao, K.; Revill, K.; Bonal, D.; Miltiadous, O.; Zhang, Z.; Hoshida, Y.; et al. Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma. Nat. Commun. 2015, 6, 6087. [Google Scholar] [CrossRef]
- Farshidfar, F.; Zheng, S.; Gingras, M.C.; Newton, Y.; Shih, J.; Robertson, A.G.; Hinoue, T.; Hoadley, K.A.; Gibb, E.A.; Roszik, J.; et al. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles. Cell Rep. 2017, 18, 2780–2794. [Google Scholar] [CrossRef] [PubMed]
- Nakamura, H.; Arai, Y.; Totoki, Y.; Shirota, T.; Elzawahry, A.; Kato, M.; Hama, N.; Hosoda, F.; Urushidate, T.; Ohashi, S.; et al. Genomic spectra of biliary tract cancer. Nat. Genet. 2015, 47, 1003–1010. [Google Scholar] [CrossRef] [PubMed]
- Roa, I.; de Toro, G.; Schalper, K.; de Aretxabala, X.; Churi, C.; Javle, M. Overexpression of the HER2/neu Gene: A New Therapeutic Possibility for Patients with Advanced Gallbladder Cancer. Gastrointest. Cancer Res. 2014, 7, 42–48. [Google Scholar] [PubMed]
- Weinberg, B.A.; Xiu, J.; Lindberg, M.R.; Shields, A.F.; Hwang, J.J.; Poorman, K.; Salem, M.E.; Pishvaian, M.J.; Holcombe, R.F.; Marshall, J.L.; et al. Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets. J. Gastrointest. Oncol. 2019, 10, 652–662. [Google Scholar] [CrossRef]
- Javle, M.; Rashid, A.; Churi, C.; Kar, S.; Zuo, M.; Eterovic, A.K.; Nogueras-Gonzalez, G.M.; Janku, F.; Shroff, R.T.; Aloia, T.A.; et al. Molecular characterization of gallbladder cancer using somatic mutation profiling. Hum. Pathol. 2014, 45, 701–708. [Google Scholar] [CrossRef]
- Jiao, Y.; Pawlik, T.M.; Anders, R.A.; Selaru, F.M.; Streppel, M.M.; Lucas, D.J.; Niknafs, N.; Guthrie, V.B.; Maitra, A.; Argani, P.; et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat. Genet. 2013, 45, 1470–1473. [Google Scholar] [CrossRef]
- Li, M.; Zhang, Z.; Li, X.; Ye, J.; Wu, X.; Tan, Z.; Liu, C.; Shen, B.; Wang, X.A.; Wu, W.; et al. Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway. Nat. Genet. 2014, 46, 872–876. [Google Scholar] [CrossRef]
- Narayan, R.R.; Creasy, J.M.; Goldman, D.A.; Gonen, M.; Kandoth, C.; Kundra, R.; Solit, D.B.; Askan, G.; Klimstra, D.S.; Basturk, O.; et al. Regional differences in gallbladder cancer pathogenesis: Insights from a multi-institutional comparison of tumor mutations. Cancer 2019, 125, 575–585. [Google Scholar] [CrossRef]
- Vivaldi, C.; Fornaro, L.; Ugolini, C.; Niccoli, C.; Musettini, G.; Pecora, I.; Cacciato Insilla, A.; Salani, F.; Pasquini, G.; Catanese, S.; et al. HER2 Overexpression as a Poor Prognostic Determinant in Resected Biliary Tract Cancer. Oncologist 2020, 25, 886–893. [Google Scholar] [CrossRef]
- Hidaka, E.; Yanagisawa, A.; Seki, M.; Takano, K.; Setoguchi, T.; Kato, Y. High frequency of K-ras mutations in biliary duct carcinomas of cases with a long common channel in the papilla of Vater. Cancer Res. 2000, 60, 522–524. [Google Scholar]
- Hanada, K.; Tsuchida, A.; Iwao, T.; Eguchi, N.; Sasaki, T.; Morinaka, K.; Matsubara, K.; Kawasaki, Y.; Yamamoto, S.; Kajiyama, G. Gene mutations of K-ras in gallbladder mucosae and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct. Am. J. Gastroenterol. 1999, 94, 1638–1642. [Google Scholar] [CrossRef]
- Masuhara, S.; Kasuya, K.; Aoki, T.; Yoshimatsu, A.; Tsuchida, A.; Koyanagi, Y. Relation between K-ras codon 12 mutation and p53 protein overexpression in gallbladder cancer and biliary ductal epithelia in patients with pancreaticobiliary maljunction. J. Hepatobiliary Pancreat. Surg. 2000, 7, 198–205. [Google Scholar] [CrossRef]
- Wistuba, I.I.; Sugio, K.; Hung, J.; Kishimoto, Y.; Virmani, A.K.; Roa, I.; Albores-Saavedra, J.; Gazdar, A.F. Allele-specific mutations involved in the pathogenesis of endemic gallbladder carcinoma in Chile. Cancer Res. 1995, 55, 2511–2515. [Google Scholar]
- Wistuba, I.I.; Gazdar, A.F.; Roa, I.; Albores-Saavedra, J. p53 protein overexpression in gallbladder carcinoma and its precursor lesions: An immunohistochemical study. Hum. Pathol. 1996, 27, 360–365. [Google Scholar] [CrossRef]
- Creasy, J.M.; Goldman, D.A.; Dudeja, V.; Lowery, M.; Cercek, A.; Balachandran, V.P.; Allen, P.J.; DeMatteo, R.P.; Kingham, T.P.; D’Angelica, M.I.; et al. Systemic Chemotherapy Combined with Resection for Locally Advanced Gallbladder Carcinoma: Surgical and Survival Outcomes. J. Am. Coll. Surg. 2017, 224, 906–916. [Google Scholar] [CrossRef]
- Shroff, R.T.; Javle, M.M.; Xiao, L.; Kaseb, A.O.; Varadhachary, G.R.; Wolff, R.A.; Raghav, K.P.S.; Iwasaki, M.; Masci, P.; Ramanathan, R.K.; et al. Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA Oncol. 2019, 5, 824–830. [Google Scholar] [CrossRef]
- Jarnagin, W.R.; Ruo, L.; Little, S.A.; Klimstra, D.; D’Angelica, M.; DeMatteo, R.P.; Wagman, R.; Blumgart, L.H.; Fong, Y. Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: Implications for adjuvant therapeutic strategies. Cancer 2003, 98, 1689–1700. [Google Scholar] [CrossRef]
- Primrose, J.N.; Fox, R.P.; Palmer, D.H.; Malik, H.Z.; Prasad, R.; Mirza, D.; Anthony, A.; Corrie, P.; Falk, S.; Finch-Jones, M.; et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): A randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019, 20, 663–673. [Google Scholar] [CrossRef]
- Edeline, J.; Benabdelghani, M.; Bertaut, A.; Watelet, J.; Hammel, P.; Joly, J.P.; Boudjema, K.; Fartoux, L.; Bouhier-Leporrier, K.; Jouve, J.L.; et al. Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study. J. Clin. Oncol. 2019, 37, 658–667. [Google Scholar] [CrossRef]
- Ben-Josef, E.; Guthrie, K.A.; El-Khoueiry, A.B.; Corless, C.L.; Zalupski, M.M.; Lowy, A.M.; Thomas, C.R., Jr.; Alberts, S.R.; Dawson, L.A.; Micetich, K.C.; et al. SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma. J. Clin. Oncol. 2015, 33, 2617–2622. [Google Scholar] [CrossRef]
- Valle, J.; Wasan, H.; Palmer, D.H.; Cunningham, D.; Anthoney, A.; Maraveyas, A.; Madhusudan, S.; Iveson, T.; Hughes, S.; Pereira, S.P.; et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N. Engl. J. Med. 2010, 362, 1273–1281. [Google Scholar] [CrossRef]
- Lamarca, A.; Palmer, D.H.; Wasan, H.S.; Ross, P.J.; Ma, Y.T.; Arora, A.; Falk, S.; Gillmore, R.; Wadsley, J.; Patel, K.; et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): A phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021, 22, 690–701. [Google Scholar] [CrossRef]
- Yoo, C.; Kim, K.P.; Jeong, J.H.; Kim, I.; Kang, M.J.; Cheon, J.; Kang, B.W.; Ryu, H.; Lee, J.S.; Kim, K.W.; et al. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): A multicentre, open-label, randomised, phase 2b study. Lancet Oncol. 2021, 22, 1560–1572. [Google Scholar] [CrossRef]
- Williams, K.J.; Picus, J.; Trinkhaus, K.; Fournier, C.C.; Suresh, R.; James, J.S.; Tan, B.R. Gemcitabine with carboplatin for advanced biliary tract cancers: A phase II single institution study. HPB 2010, 12, 418–426. [Google Scholar] [CrossRef][Green Version]
- Kim, S.T.; Kang, J.H.; Lee, J.; Lee, H.W.; Oh, S.Y.; Jang, J.S.; Lee, M.A.; Sohn, B.S.; Yoon, S.Y.; Choi, H.J.; et al. Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: A multicenter, open-label, randomized, phase III, noninferiority trial. Ann. Oncol. 2019, 30, 788–795. [Google Scholar] [CrossRef]
- Malka, D.; Cervera, P.; Foulon, S.; Trarbach, T.; de la Fouchardiere, C.; Boucher, E.; Fartoux, L.; Faivre, S.; Blanc, J.F.; Viret, F.; et al. Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): A randomised, open-label, non-comparative phase 2 trial. Lancet Oncol. 2014, 15, 819–828. [Google Scholar] [CrossRef]
- Chen, J.S.; Hsu, C.; Chiang, N.J.; Tsai, C.S.; Tsou, H.H.; Huang, S.F.; Bai, L.Y.; Chang, I.C.; Shiah, H.S.; Ho, C.L.; et al. A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer. Ann. Oncol. 2015, 26, 943–949. [Google Scholar] [CrossRef]
- Lubner, S.J.; Mahoney, M.R.; Kolesar, J.L.; Loconte, N.K.; Kim, G.P.; Pitot, H.C.; Philip, P.A.; Picus, J.; Yong, W.P.; Horvath, L.; et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: A phase II Consortium study. J. Clin. Oncol. 2010, 28, 3491–3497. [Google Scholar] [CrossRef]
- Iyer, R.V.; Pokuri, V.K.; Groman, A.; Ma, W.W.; Malhotra, U.; Iancu, D.M.; Grande, C.; Saab, T.B. A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer. Am. J. Clin. Oncol. 2018, 41, 649–655. [Google Scholar] [CrossRef]
- Santoro, A.; Gebbia, V.; Pressiani, T.; Testa, A.; Personeni, N.; Arrivas Bajardi, E.; Foa, P.; Buonadonna, A.; Bencardino, K.; Barone, C.; et al. A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: The VanGogh study. Ann. Oncol. 2015, 26, 542–547. [Google Scholar] [CrossRef]
- Makower, D.; Rozenblit, A.; Kaufman, H.; Edelman, M.; Lane, M.E.; Zwiebel, J.; Haynes, H.; Wadler, S. Phase II clinical trial of intralesional administration of the oncolytic adenovirus ONYX-015 in patients with hepatobiliary tumors with correlative p53 studies. Clin. Cancer Res. 2003, 9, 693–702. [Google Scholar] [PubMed]
- Peck, J.; Wei, L.; Zalupski, M.; O’Neil, B.; Villalona Calero, M.; Bekaii-Saab, T. HER2/neu may not be an interesting target in biliary cancers: Results of an early phase II study with lapatinib. Oncology 2012, 82, 175–179. [Google Scholar] [CrossRef]
- Ramanathan, R.K.; Belani, C.P.; Singh, D.A.; Tanaka, M.; Lenz, H.J.; Yen, Y.; Kindler, H.L.; Iqbal, S.; Longmate, J.; Mack, P.C.; et al. A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer. Cancer Chemother. Pharmacol. 2009, 64, 777–783. [Google Scholar] [CrossRef] [PubMed]
- Javle, M.M.; Oh, D.-Y.; Ikeda, M.; Yong, W.-P.; McIntyre, N.; Lindmark, B.; McHale, M. Results from TreeTopp: A randomized phase II study of the efficacy and safety of varlitinib plus capecitabine versus placebo in second-line (2L) advanced or metastatic biliary tract cancer (BTC). J. Clin. Oncol. 2020, 38, 4597. [Google Scholar] [CrossRef]
- Javle, M.; Borad, M.J.; Azad, N.S.; Kurzrock, R.; Abou-Alfa, G.K.; George, B.; Hainsworth, J.; Meric-Bernstam, F.; Swanton, C.; Sweeney, C.J.; et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): A multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021, 22, 1290–1300. [Google Scholar] [CrossRef]
- Meric-Bernstam, F.; Hanna, D.L.; El-Khoueiry, A.B.; Kang, Y.-K.; Oh, D.-Y.; Chaves, J.M.; Rha, S.Y.; Hamilton, E.P.; Pant, S.; Javle, M.M.; et al. Zanidatamab (ZW25) in HER2-positive biliary tract cancers (BTCs): Results from a phase I study. J. Clin. Oncol. 2021, 39, 299. [Google Scholar] [CrossRef]
- Harding, J.J.; Cleary, J.M.; Quinn, D.I.; Braña, I.; Moreno, V.; Borad, M.J.; Loi, S.; Spanggaard, I.; Park, H.; Ford, J.M.; et al. Targeting HER2 (ERBB2) mutation-positive advanced biliary tract cancers with neratinib: Results from the phase II SUMMIT ‘basket’ trial. J. Clin. Oncol. 2021, 39, 320. [Google Scholar] [CrossRef]
- Ohba, A.; Morizane, C.; Ueno, M.; Kobayashi, S.; Kawamoto, Y.; Komatsu, Y.; Ikeda, M.; Sasaki, M.; Okano, N.; Furuse, J.; et al. Multicenter phase II study of trastuzumab deruxtecan (DS-8201) for HER2-positive unresectable or recurrent biliary tract cancer: HERB trial. J. Clin. Oncol. 2020, 38, TPS4654. [Google Scholar] [CrossRef]
- Chang, A.E.; Shahda, S.; Harris, W.P.; Cohen, S.; Coveler, A.L.; O’Neil, B.H.; Gadi, V.K.; Hibbert, R.; Lee, H.H.; Younger, A.; et al. Phase I/IB multicenter study of afatinib in combination with capecitabine in patients (pts) with refractory solid tumors and pancreatico-biliary cancers. J. Clin. Oncol. 2017, 35, TPS515. [Google Scholar] [CrossRef]
- Javle, M.; Bekaii-Saab, T.; Jain, A.; Wang, Y.; Kelley, R.K.; Wang, K.; Kang, H.C.; Catenacci, D.; Ali, S.; Krishnan, S.; et al. Biliary cancer: Utility of next-generation sequencing for clinical management. Cancer 2016, 122, 3838–3847. [Google Scholar] [CrossRef]
- Piha-Paul, S.A.A.; Xu, B.; Janku, F.; Dumbrava, E.E.; Fu, S.; Karp, D.D.; Meric-Bernstam, F.; Hong, D.S.; Ahnert, J.R.; Tsimberidou, A.M.; et al. Phase I study of TT-00420, a multiple kinase inhibitor, as a single agent in advanced solid tumors. J. Clin. Oncol. 2021, 39, 3090. [Google Scholar] [CrossRef]
- Goeppert, B.; Frauenschuh, L.; Renner, M.; Roessler, S.; Stenzinger, A.; Klauschen, F.; Warth, A.; Vogel, M.N.; Mehrabi, A.; Hafezi, M.; et al. BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma. Mod. Pathol. 2014, 27, 1028–1034. [Google Scholar] [CrossRef]
- Bridgewater, J.; Lopes, A.; Beare, S.; Duggan, M.; Lee, D.; Ricamara, M.; McEntee, D.; Sukumaran, A.; Wasan, H.; Valle, J.W. A phase 1b study of Selumetinib in combination with Cisplatin and Gemcitabine in advanced or metastatic biliary tract cancer: The ABC-04 study. BMC Cancer 2016, 16, 153. [Google Scholar] [CrossRef]
- Lowery, M.A.; Bradley, M.; Chou, J.F.; Capanu, M.; Gerst, S.; Harding, J.J.; Dika, I.E.; Berger, M.; Zehir, A.; Ptashkin, R.; et al. Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers. Clin. Cancer Res. 2019, 25, 937–945. [Google Scholar] [CrossRef]
- Kim, J.W.; Lee, K.H.; Kim, J.W.; Suh, K.J.; Nam, A.R.; Bang, J.H.; Bang, Y.J.; Oh, D.Y. Enhanced antitumor effect of binimetinib in combination with capecitabine for biliary tract cancer patients with mutations in the RAS/RAF/MEK/ERK pathway: Phase Ib study. Br. J. Cancer 2019, 121, 332–339. [Google Scholar] [CrossRef]
- Wainberg, Z.A.; Lassen, U.N.; Elez, E.; Italiano, A.; Curigliano, G.; Braud, F.G.D.; Prager, G.; Greil, R.; Stein, A.; Fasolo, A.; et al. Efficacy and safety of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated biliary tract cancer (BTC): A cohort of the ROAR basket trial. J. Clin. Oncol. 2019, 37, 187. [Google Scholar] [CrossRef]
- Subbiah, V.; Lassen, U.; Elez, E.; Italiano, A.; Curigliano, G.; Javle, M.; de Braud, F.; Prager, G.W.; Greil, R.; Stein, A.; et al. Dabrafenib plus trametinib in patients with BRAF(V600E)-mutated biliary tract cancer (ROAR): A phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020, 21, 1234–1243. [Google Scholar] [CrossRef]
- Rashid, A.; Ueki, T.; Gao, Y.T.; Houlihan, P.S.; Wallace, C.; Wang, B.S.; Shen, M.C.; Deng, J.; Hsing, A.W. K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: A population-based study in China. Clin. Cancer Res. 2002, 8, 3156–3163. [Google Scholar]
- Piha-Paul, S.A.; Oh, D.Y.; Ueno, M.; Malka, D.; Chung, H.C.; Nagrial, A.; Kelley, R.K.; Ros, W.; Italiano, A.; Nakagawa, K.; et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies. Int. J. Cancer 2020, 147, 2190–2198. [Google Scholar] [CrossRef]
- Kim, R.D.; Chung, V.; Alese, O.B.; El-Rayes, B.F.; Li, D.; Al-Toubah, T.E.; Schell, M.J.; Zhou, J.M.; Mahipal, A.; Kim, B.H.; et al. A Phase 2 Multi-institutional Study of Nivolumab for Patients with Advanced Refractory Biliary Tract Cancer. JAMA Oncol. 2020, 6, 888–894. [Google Scholar] [CrossRef]
- Oh, D.Y.; Chen, L.T.; He, A.R.; Okusaka, T.; Qin, S.; Chin, S.; Rokutanda, N.; Uchinda, H.; Vogel, A.; Valle, J.W.; et al. A phase III, randomized, double-blind, placebo-controlled, international study of durvalumab in combination with gemcitabine plus cisplatin for patients with advanced biliary tract cancers: TOPAZ-1. Ann. Oncol. 2019, 30, 319. [Google Scholar] [CrossRef]
- Oh, D.-Y.; He, A.R.; Qin, S.; Chen, L.-T.; Okusaka, T.; Vogel, A.; Kim, J.W.; Suksombooncharoen, T.; Lee, M.A.; Kitano, M.; et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. J. Clin. Oncol. 2022, 40, 378. [Google Scholar] [CrossRef]
Authors | Phase | Treatment | Median RFS (Months) | Median OS (Months) |
---|---|---|---|---|
Primrose [58] BILCAP study | 3 | capecitabine vs. observation | 24.4 vs. 17.5 (p = 0.03) | 51.1 vs. 36.4 (p = 0.097) |
Edeline [59] PRODIGE 12-ACCORD 18 study | 3 | GEMOX vs. observation | 30.4 vs. 18.5 (p = 0.48) | 75.8 vs. 50.8 (p = 0.74) |
Ben-Josef [60] SWOG S0809 study | 2 | Gemcitabine and capecitabine followed by capecitabine with RT | 26 | 35 |
Phase | NCT Number | Tumor Type | Line | Treatment | Location |
---|---|---|---|---|---|
2/3 | NCT02867865 | Locally advanced gallbladder cancers | 1st | Neoadjuvant GEMCIS vs. neoadjuvant radiation with weekly gemcitabine | India |
2/3 | NCT04559139 | Stage II-III gallbladder cancers | 1st | Neoadjuvant GEMCIS, resection then adjuvant GEMCIS vs. resection then adjuvant GEMCIS | United States |
2 | NCT04333927 | Resected extrahepatic cholangiocarcinoma and gallbladder cancers | 1st | Camrelizumab, then capecitabine with radiotherapy vs. observation | China |
1 | NCT03257761 | Unresectable liver, pancreatic, BTCs | 2nd | Guadecitabine and durvalumab | United States |
3 | NCT03673072 | BTCs | 1st | Neoadjuvant GEMCIS followed by liver resection vs. upfront liver resection | Germany |
2 | NCT03833661 | Locally advanced BTCs | 2nd | bintrafusp alfa, a bifunctional anti-PD-L1/TGFβ trap | United States, Europe, Asia |
2 | NCT03473574 | Unresectable BTCs | 1st | durvalumab/tremelimumab/gemcitabine vs. durvalumab/tremeliumab/GEMCIS vs. GEMCIS vs. durvalumab/GEMCIS | Germany |
2 | NCT03043547 | Locally advanced BTCs | 2nd | Liposomal irinotecan and 5-FU vs. 5-FU | Germany |
3 | NCT02170090 | Resected BTCs | 1st | Adjuvant GEMCIS vs. capecitabine | Europe, Australia |
2 | NCT04466891 | Locally advanced HER2-amplified BTCs | 2nd | Zanidatamab, a HER2-targeted bispecific antibody | United States, Europe, Asia |
2/3 | NCT04066491 | Locally advanced BTCs | 1st | bintrafusp alfa with GEMCIS vs. GEMCIS | United States, South America, Australia, Asia, Europe |
3 | NCT03779035 | Resected BTCs | 1st | Adjuvant GEMCIS vs. capecitabine | China |
1/2 | NCT04203160 | Locally advanced BTCs | 1st | Devimistat, anti-mitochondrial inhibitor, with GEMCIS vs. GEMCIS | United States |
2 | NCT04308174 | BTCs | 1st | Neoadjuvant durvalumab with GEMCIS vs. neoadjuvant GEMCIS | Korea |
2 | NCT02151084 | Locally advanced or metastatic BTCs | 1st | Selumetinib with GEMCIS vs. GEMCIS | Canada |
2 | NCT02834013 | Locally advanced gallbladder cancers | 2nd | Nivolumab and ipilimumab | United States |
2 | NCT03260712 | Locally advanced or metastatic BTCs | 1st | Pembrolizumab with GEMCIS | Europe |
2 | NCT03801083 | Locally advanced or metastatic BTCs | 1st and 2nd | Tumor infiltrating lymphocytes and IL-2 | United States |
1/2 | NCT03733990 | Locally advanced or metastatic BTCs, melanoma, ER+ breast, gastric, ovarian, pancreatic, colorectal, liver or anaplastic thyroid cancers | 2nd | FP-1305, a CLEVER-1 inhibitor | United States, Europe |
2 | NCT04856761 | Resected BTCs | 1st | Adjuvant capecitabine vs. adjuvant S1 | China |
1 | NCT04495296 | Metastatic solid tumors | 2nd | TST001, an anti-Claudin 18.2 monoclonal antibody | China |
2 | NCT03796429 | Locally advanced BTCs | 1st | Toripalimab with GEMCIS | China |
2 | NCT04059562 | Locally advanced or metastatic BTCs | 2nd | Trifluridine/tipiracil with irinotecan | Germany |
2 | NCT04969887 | Intrahepatic cholangiocarcinomas and gallbladder cancers | 1st and 2nd | Ipilimumab and nivolumab | Australia |
1/2 | NCT05000294 | Metastatic BTCs | 2nd | Atezolizumab with tivozanib | United States |
2 | NCT03278106 | Advanced BTCs | 2nd | Trifluridine/tipiracil | United States |
3 | NCT03768414 | Metastatic or locally advanced BTCs | 1st | GEMCIS vs. GEMCIS with nab-paclitaxel | United States |
1/2 | NCT04742959 | Metastatic BTCs | 2nd | TT-00420, a spectrum-selective multi-kinase inhibitor | United States |
2 | NCT04383210 | NRG1 gene fusion positive advanced BTCs | 1st and 2nd | Seribantumab, an anti-Her3 monoclonal antibody | United States |
1/2 | NCT04426669 | Metastatic gastrointestinal epithelial cancers | 2nd | CISH inactivated tumor infiltrating lymphocytes and IL-2 | United States |
2 | NCT04941287 | Unresectable BTCs | 2nd | Atezolizumab with varlilumab, an anti-CD27 antibody vs. atezolizumab with varlilumab and cobimetinib | United States |
1/2 | NCT05086692 | Advanced solid tumors | Any | MDNA11, an engineered IL-2 | Australia |
1/2 | NCT04430738 | HER2-positive GI cancers | 1st | Tucatinib with trastuzumab and FOLFOX vs. tucatinib with trastuzumab and CAPOX | United States |
3 | NCT04924062 and NCT04924062 | Advanced or unresectable BTCs | 1st | Pembrolizumab with GEMCIS vs. GEMCIS | Global |
2 | NCT04211168 | Advanced BTCs | 2nd | Toripalimab with lenvatinib | China |
2 | NCT02703714 | Advanced BTCs | Any | Pembrolizumab with G-CSF | United States |
1 | NCT03985072 | Advanced solid tumors | 2nd | ANDES-1537, an antisense oligonucleotide | Chile |
1 | NCT04853017 | KRAS mutated solid tumor | Any | ELI-002 2P, mix of modified KRAS peptides | United States |
1/2 | NCT04068194 | Advanced or metastatic Hepatobiliary malignancies | 2nd | RT with avelumab vs. RT with avelumab and peposertib, a DNA-PK inhibitor | United States |
2 | NCT02520141 | Locally advanced or metastatic BTCs | 2nd | Ramucirumab | United States |
1 | NCT02495896 | Advanced solid tumors | Any | sEphB4-HSA fusion protein with gemcitabine and nab-paclitaxel vs. sEphB4-HSA fusion protein with docetaxel vs. sEphB4-HSA fusion protein with GEMCIS | United States |
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Hu, Z.I.; Lim, K.-H. Evolving Paradigms in the Systemic Treatment of Advanced Gallbladder Cancer: Updates in Year 2022. Cancers 2022, 14, 1249. https://doi.org/10.3390/cancers14051249
Hu ZI, Lim K-H. Evolving Paradigms in the Systemic Treatment of Advanced Gallbladder Cancer: Updates in Year 2022. Cancers. 2022; 14(5):1249. https://doi.org/10.3390/cancers14051249
Chicago/Turabian StyleHu, Zishuo Ian, and Kian-Huat Lim. 2022. "Evolving Paradigms in the Systemic Treatment of Advanced Gallbladder Cancer: Updates in Year 2022" Cancers 14, no. 5: 1249. https://doi.org/10.3390/cancers14051249
APA StyleHu, Z. I., & Lim, K.-H. (2022). Evolving Paradigms in the Systemic Treatment of Advanced Gallbladder Cancer: Updates in Year 2022. Cancers, 14(5), 1249. https://doi.org/10.3390/cancers14051249