Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials
Abstract
:1. Introduction
2. Chemotherapy
3. Targeted Therapy
3.1. FGFR2 Fusions
3.2. IDH1/2 Mutations and PARP
4. EGFR/HER2
5. RAF/MEK
6. c-MET
7. PI3K/AKT/mTOR
8. Anti-Angiogenesis Agents
9. NTRK
10. Immune Checkpoint Inhibitors
11. Complementary Agents
12. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug(s) | Study | Case (n) | Target | ORR (%) | SD (%) | PFS (mos) | OS (mos) |
---|---|---|---|---|---|---|---|
chemotherapy | |||||||
mFOLFOX vs. ASC [22] | ABC06 Phase III | 162 (81 vs. 81) | - | 4% | 28% | 4 | 6.2 |
S-1 [24] | Japan Phase II | 40 | - | 7.5% | 55% | 2.5 | 6.8 |
FOLFIRINOX [27] | Phase II | 30 | - | 10% | 57% | 6.2 | 10.7 |
Targeted therapy | |||||||
Pemigatinib [34] | FIGHT202Phase II | 107 * | FGFR1-3 VEGFR2 | 35.5% | 46.5% | 6.9 | 21.1 |
Infigratinib (BGJ398) [36] | Phase II | 71 * | FGFR1-3 | 26.9% & | 56.7% | 6.8 | 12.5 |
Derazantinib (ARQ087) [38] | Phase I/II | 30 * | FGFR1-3 RET, PDGFR, KIT, SRC | 20.7% | 62.1% | 5.7 | - |
Fuibatinib (TAS-120) [39] | Phase I/II | 28 * | FGFR1-4 | 25% | 54% | - | - |
Ivosidenib vs. placebo [50] | ClarIDHy Phase III | 185 ** (124 vs. 61) | Mutant IDH1 | 2.4% | 50.8% | 2.7 | 10.8 |
Dabrafenib + trametinib [88] | ROAR Phase II | 43 *** | BRAFV600E | 51% | - | 9 | 14 |
Regorafenib vs. placebo [108] | REACHIN Phase II | 66(33 vs. 33) | VEGF1-3, PDGFR, FGFR | 0% | 74% | 3 | 5.3 |
Immunotherapy | |||||||
Pembrolizumab [127] | KN-158 Phase II | 104 | PD-1 | 5.8% | - | 2 | 7.4 |
Nivolumab [131] | Korea Phase II | 54 | PD-1 | 22% $ 11% # | - | 3.7 | 14.2 |
Durvalumab + Tremelimumb [134] | Phase I | 42 (D) 65 (D + T) | PD-L1 + CTLA-4 | 5% (D) 11% (D + T) | - | - | 8.1 (D) 10.1 (T + D) |
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Chiang, N.-J.; Chen, L.-T.; Shan, Y.-S.; Yeh, C.-N.; Chen, M.-H. Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials. Biomolecules 2021, 11, 97. https://doi.org/10.3390/biom11010097
Chiang N-J, Chen L-T, Shan Y-S, Yeh C-N, Chen M-H. Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials. Biomolecules. 2021; 11(1):97. https://doi.org/10.3390/biom11010097
Chicago/Turabian StyleChiang, Nai-Jung, Li-Tzong Chen, Yan-Shen Shan, Chun-Nan Yeh, and Ming-Huang Chen. 2021. "Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials" Biomolecules 11, no. 1: 97. https://doi.org/10.3390/biom11010097
APA StyleChiang, N.-J., Chen, L.-T., Shan, Y.-S., Yeh, C.-N., & Chen, M.-H. (2021). Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials. Biomolecules, 11(1), 97. https://doi.org/10.3390/biom11010097