The Role of HER2 Status in the Biliary Tract Cancers
Abstract
:Simple Summary
Abstract
1. Introduction
2. Prognostic Role of HER2 Status in BTC
3. HER2 Alterations in BTC
4. Resistance to Anti-HER2 Therapies
5. Completed and Ongoing Clinical Trials
6. Conclusions—Concluding Remarks and Future Perspectives
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Primary Tumor Site | Frequency of HER2 Alteration |
---|---|
Intrahepatic cholangiocarcinoma | 5.8% |
Extrahepatic cholangiocarcinoma | 13.9% |
Gallbladder cancer | 36.4% |
Ampulla of Vater | 18.2% |
Type of HER2 Alteration | Frequency of HER2 Alteration 100% (n = 18) |
---|---|
Point mutation | 27.8% (n = 5) |
Gene amplification | 61.1% (n = 11) |
Point mutation and gene amplification | 11.1% (n = 2) |
Primary Tumor Site | Frequency of HER2 Alteration | Type of HER2 Alteration |
---|---|---|
Intrahepatic CCA | 4.2% | Point mutation (23.8%) and copy number alteration (66.6%) |
Extrahepatic CCA | 9.7% | Point mutation (53.6%) and copy number alteration (41.2%) |
Clinical Trial | Drug | Patient Characteristics | Study Phase | Recruitment Status | Primary Endpoint | Results |
---|---|---|---|---|---|---|
NCT00478140 | Trastuzumab | Previously treated, locally advanced or metastatic gallbladder cancer or bile duct cancer that cannot be removed by surgery | II | Terminated due to slow accrual | ORR, DOR | Terminated |
NCT00107536 | Lapatinib ditosylate | Previously treated, unresectable liver or biliary tract cancer (BTC) | II | Completed | ORR, PFS, AEs, median OS, OS | Completed |
NCT04466891 (HERIZON-BTC-01) | Zanidatamab | Previously treated, advanced or metastatic HER2-amplified BTCs | II | Active, not recruiting | ORR, DOR, DCR, PFS, OS, AEs | Not recruiting |
NCT04329429 | RC48-ADC | Previously treated, locally advanced or metastatic HER2 overexpressed BTC who have failed first-line chemotherapy | II | Recruiting | ORR, DOR, PFS, OS, DCR, AEs | Active |
NCT03929666 | ZW25 (Zanidatamab) Capecitabine Cisplatin Fluorouracil Leucovorin Oxaliplatin Bevacizumab Gemcitabine | Previously treated, unresectable, locally advanced, recurrent, or metastatic HER2-expressing BTC | II | Recruiting | DLT, AEs, ORR | Active |
NCT04837508 | MRG002 ADC | Previously treated, unresectable locally advanced or metastatic BTC patients who have progressed during or relapsed after at least one prior stand therapy | II | Recruiting | ORR | Active |
NCT04722133 | Herzuma (Trastuzumab-pkrb) mFOLFOX | Previously treated, HER2-positive advanced/metastatic/nonresectable BTC | II | Recruiting | ORR, PFS, DCR, OS, AEs | Active |
NCT05417230 | RC48-ADC Envafolimab (anti-PDL1) | Previously treated, locally advanced or metastatic BTC with positive HER-2 | II | Not yet recruiting | ORR, PFS, DCR, OS, AEs | Active |
NCT04482309 (DESTINY-PanTumor02) | Trastuzumab Deruxtecan (T-DXd, DS-8201a) | HER2-overexpressing tumor-specific cohorts including BTC | II | Active, not recruiting | ORR, PFS, DCR, OS, AEs | Active, not recruiting |
NCT05540483 (RIGHT) | RC-48 GLS-010 (anti-PD1) | Previously treated unresectable BTC | II | Recruiting | ORR, AEs, PFS, DOR, DCR, OS | Active |
NCT04450732 | GQ1001 | Previously treated, HER2-positive advanced solid tumors | I | Recruiting | DLT, AEs, maximum tolerated dose (MTD) | Active |
NCT02451553 | Afatinib dimaleate Capecitabine | Previously treated, advanced refractory solid tumors, pancreatic cancer, or biliary cancer | I | Completed | DLT, AEs, MTD | Completed |
NCT04660929 | CT-0508 (CAR macrophages) | Previously treated, HER2-overexpressing solid tumors | I | Recruiting | AEs, ORR, PFS | Active |
NCT04579380 | Tucatinib Trastuzumab | Previously treated, locally advanced unresectable or metastatic solid tumors driven by HER2 alterations | II | Recruiting | cORR, DCR, PFS, OS, AEs | Active |
NCT04278144 | BDC-1001 (immune stimulating antibody conjugate, ISAC) Nivolumab | HER2-overexpressing advanced malignancies | I/II | Recruiting | AEs, DLT, ORR, DOR, DCR, PFS | Active |
NCT04460456 | SBT6050 (ISAC) Pembrolizumab Cemiplimab | HER2 expressing or amplified advanced malignancies | I | Active, not recruiting | DLT, AEs, ORR, DOR, DCR, PFS | Active, not recruiting |
NCT05150691 | DB-1303 | HER2 expressing advanced solid tumors | I/II | Recruiting | DLT, ORR, AEs | Active |
NCT00478140 | Trastuzumab | HER2/neu-positive advanced gallbladder or biliary tract cancer | II | Terminated (Due to slow accrual) | ORR, DCR, OS | Terminated |
NCT02999672 | Trastuzumab emtansine | HER2 overexpressing solid tumors | II | Completed | OS, PFS, AEs | Completed |
NCT04430738 | Tucatinib Trastuzumab FOLFOX CAPOX Pembrolizumab | HER2+ gastrointestinal cancers | I/II | Recruiting | DLT, AEs, ORR, DOR, PFS, OS | Active |
NCT03613168 (BILHER) | Trastuzumab GEMCIS | HER2+ biliary tract cancer | II | Completed | RR, PFS, OS | Completed |
NCT00101036 | Lapatinib ditosylate | Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery | II | Completed | ORR, OS, PFS | Completed |
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Ayasun, R.; Ozer, M.; Sahin, I. The Role of HER2 Status in the Biliary Tract Cancers. Cancers 2023, 15, 2628. https://doi.org/10.3390/cancers15092628
Ayasun R, Ozer M, Sahin I. The Role of HER2 Status in the Biliary Tract Cancers. Cancers. 2023; 15(9):2628. https://doi.org/10.3390/cancers15092628
Chicago/Turabian StyleAyasun, Ruveyda, Muhammet Ozer, and Ilyas Sahin. 2023. "The Role of HER2 Status in the Biliary Tract Cancers" Cancers 15, no. 9: 2628. https://doi.org/10.3390/cancers15092628