Advanced Biliary Tract Cancer: Exploration of Third-Line and Other Therapeutic Areas After Failure of Chemotherapy Alone
Abstract
Simple Summary
Abstract
1. Introduction
2. Tumor Biomarkers
3. Limitations
4. First-Line and Second-Line Treatment
5. Identification of Therapeutic Targets
6. Clinical Trials in Treatment-Resistant Settings
6.1. Chemotherapy
6.2. Targeted Therapy
6.3. Immunotherapy
6.4. Combination of Targeted Therapy and Immunotherapy
6.5. Novel Therapeutic Approaches
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Regimen | Applicable Population | Design | mOS | Hazard Ratio p Value | mPFS | Hazard Ratio p Value | ORR | p Value | Source |
---|---|---|---|---|---|---|---|---|---|
Durvalumab + GEM + DDP | U/M | Durvalumab + GEM + DDP GEM + DDP | 12.9 m 11.3 m | HR = 0.80 p = 0.021 | 7.2 m 5.7 m | HR = 0.75 p = 0.001 | 26.7% 18.7% | p = 0.007 | TOPAZ-1 |
Pembrolizumab + GEM + DDP | U/M | Pembrolizumab + GEM + DDP GEM + DDP | 12.7 m 10.9 m | HR = 0.83 p = 0.0034 | 6.3 m 5.8 m | HR = 0.86 p = 0.0038 | 29.0% 24.0% | p = 0.0029 | KEYNOTE-966 |
GEM + DDP | NI | GEM + DDP GEM | 11.7 m 8.1 m | HR = 0.64 p < 0.001 | 8.0 m 5.0 m | HR = 0.63 p < 0.001 | 26.1% 15.5% | p = 0.006 | ABC-02 |
Targeted Therapy | Patients with alterations * | Refer to Table 2 |
Biomarker | Regimen | Study Population | Treatment Group | mDoR | mPFS | mOS | ORR | DCR | Trial |
---|---|---|---|---|---|---|---|---|---|
MSI-H/dMMR | Pembrolizumab * | Pre-treated Patients | SA | N | 4.1 m | 23.5 m | 39.60% | - | KEYNOTE-158 |
NTRK Gene Fusion | Larotrectinib * | 49.3 m | 35.4 m | N | 75.00% | - | LOXO-TRK-01,NAVIGATE | ||
Entrectinib * | 20.0 m | 13.8 m | 33.8 m | 63.00% | - | STARTRK-1/2,ALKA-372-001 | |||
FGFR2 Fusion/ Rearrangement | Pemigatinib * | 7.5 m | 6.9 m | 21.1 m | 35.50% | 82.00% | FIGHT-202 | ||
Futibatinib * | 9.5 m | 8.9 m | 20.0 m | 41.70% | 82.50% | FOENIX-CCA2 | |||
Infigratinib | 5.0 m | 7.3 m | 12.2 m | 23.10% | 84.30% | CBGJ398X2204 | |||
IDH1 Mutation | Ivosidenib * | Ivosidenib PB | - | 2.7 m 1.4 m (HR = 0.37, p < 0.0001) | 10.3 m 7.5 m (HR = 0.49, p < 0.0001) | 2.4% p = 0.283 | 53.2% p < 0.0001 | ClarlDHy | |
BRAF V600E Mutation | Dabrafenib * + Trametinib * | SA | 8.7 m | 8.9 m | 13.5 m | 51% | 79% | ROAR |
Treatment Population | Treatment Strategy | Regimen | mOS | Hazard Ratio p Value | mPFS | Hazard Ratio p Value | ORR | Trail |
---|---|---|---|---|---|---|---|---|
With actionable targets | Refer to Table 2 | |||||||
Without actionable targets | FOLFOX | FOLFOX +ASC ASC | 6.2 m 5.3 m | HR = 0.69 p = 0.031 | 4.0 m 2.0 m | HR = 0.63 p = 0.006 | 5% 0 | ABC-06 |
FOLFIRI | Irinotecan +Leucovorin +5-FU | 10.6 m | - | 4.6 m | - | 15% | Phase II single-arm | |
Nab-Paclitaxel +Gemcitabine | Nab-Paclitaxel +Gemcitabine | 7-9 m | - | 3-5 m | - | 10-20% | Retrospective analysis | |
Capecitabine | Capecitabine | 5.3 m | - | 2.3 m | - | 5.60% | Retrospective analysis | |
S-1 | S-1 | 7.6 m | - | 2.7 m | - | 10% | Phase II single-arm |
Clinical Trail | N | Regimen | mOS | Hazard Ratio p Value | mPFS | Hazard Ratio p Value | ORR | p Value |
---|---|---|---|---|---|---|---|---|
chemotherapy | ||||||||
NIFTY Trial Jaewon Hyung, Ilhwan Kim et al. JAMA Oncol. 2023 [40] | 174 | nal-IRI + FU/LV PB | 8.6 m 5.3 m | HR = 0.68 p = 0.02 | 3.9 m 1.6 m | HR: 0.51 p < 0.001 | 19.3% 2.3% | p < 0.001 |
targeted therapy | ||||||||
FIGHT-202 Trial Abou-Alfa GK et al. Lancet Oncol. 2020 [29] | 146 | pemigatinib | 21.1 m | - | 6.9 m | - | 35.50% | - |
FOENIX-CCA2 Trial Goyal L et al. N. Engl. J. Med. 2023 [30] | 103 | futibatinib | 20.0 m | - | 8.9 m | - | 41.70% | - |
ClarIDHy Goyal L et al. N. Engl. J. Med. 2023 [30] | 185 | Ivosidenib PB | 10.3 m 7.5 m | HR = 0.49 p < 0.0001 | 2.7 m 1.4 m | HR: 0.37 p < 0.0001 | 2.4% 0 | - |
ROAR Trial Vivek Subbiah et al. Lancet Oncol. 2020 [42] | 43 | Dabrafenib+ trametinib | 13.5 m | - | 8.9 m | - | 51.00% | - |
Zanidatamab-related Funda Meric-Bernstam et al. Lancet Oncol. 2022 [44] | 86 | zanidatamab | - | - | 5.4 m | - | 37.00% | - |
Surufatinib-related Jianming Xu et al. Cancer 2021 [46] | 39 | surufatinib | 6.9 m | - | 3.7 m | - | 0.00% | - |
immunotherapy | ||||||||
Nivolumab-related Richard D. Kim et al. JAMA Oncol. 2020 [48] | 54 | nivolumab | 14.24 m | - | 3.68 m | - | 22.00% | - |
SWOG 1609 cohort 48 Sandip P. Patel et al. Cancer 2024 [50] | 19 | Nivolumab+ ipilimumab | 7 m | - | 1.8 m | - | 16.00% | - |
immunotherapy combined with chemotherapy | ||||||||
IMMUNOBIL PRODIGE 57 Trial Alice Boilève et al. Eur. J. Cancer 2021 [47] | 20 | Durvalumab + tremelimumab + paclitaxel PB | - | - | - | - | 10.00% | - |
immunotherapy combined with targeted therapy | ||||||||
SAGC Trial Jaewon Hyung, Ilhwan Kim et al. JAMA Oncol. 2023 [40] | 80 | Sintilimab + anlotinib + GC GC | 13.2 m 13.7 m | HR: 1.04 p = 0.895 | 8.5 m 6.3 m | HR: 0.48 p = 0.005 | 51.4% 29.4% | p = 0.033 |
SHR-1701 combined with famitinib Lixia Yi et al. Signal Transduct. Target. Ther. 2024 [52] | 27 | SHR-1701+ famitinib | 16.0 m | - | 5.1 m | - | 28.00% | - |
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Ma, L.; Yi, C. Advanced Biliary Tract Cancer: Exploration of Third-Line and Other Therapeutic Areas After Failure of Chemotherapy Alone. Cancers 2025, 17, 3268. https://doi.org/10.3390/cancers17193268
Ma L, Yi C. Advanced Biliary Tract Cancer: Exploration of Third-Line and Other Therapeutic Areas After Failure of Chemotherapy Alone. Cancers. 2025; 17(19):3268. https://doi.org/10.3390/cancers17193268
Chicago/Turabian StyleMa, Li, and Cheng Yi. 2025. "Advanced Biliary Tract Cancer: Exploration of Third-Line and Other Therapeutic Areas After Failure of Chemotherapy Alone" Cancers 17, no. 19: 3268. https://doi.org/10.3390/cancers17193268
APA StyleMa, L., & Yi, C. (2025). Advanced Biliary Tract Cancer: Exploration of Third-Line and Other Therapeutic Areas After Failure of Chemotherapy Alone. Cancers, 17(19), 3268. https://doi.org/10.3390/cancers17193268