Immunotherapy as a Promising Option for the Treatment of Advanced Chordoma: A Systemic Review
Abstract
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Search Results
3.2. Study Characteristics
3.3. Efficacy and Safety of Immunotherapy in Chordoma Patients
3.4. PD-1/PD-L1 Immune Checkpoint Inhibitors
3.5. CTLA-4 Immune Checkpoint Inhibitor
3.6. Cancer Vaccine
3.7. Other Immunomodulatory Drugs
4. Discussion
4.1. Indications and Evaluation Criteria for Immunotherapy
4.2. Cancer Vaccines
4.3. Immune Checkpoint Inhibitor
4.3.1. PD-1/PD-L1
4.3.2. CTLA-4
4.3.3. Other Targets
4.3.4. Prediction of ICIs Response
4.4. Cell Therapy
5. Limitations
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Year | Study Design | Levels of Evidence | Sample Size | Tumor Site | Treatment History | Drug | Median Treatment Time (m) | AEs | Choi’s Criteria | RECIST/irRECIST | Median PFS (m) | Median OS (m) |
---|---|---|---|---|---|---|---|---|---|---|---|---|
022 | case series | IV | 9 | 2 clival 5 spine, and 10 sacrum, | radiotherapy | pembrolizumab 200 mg | 12 | dermatologic (n = 2), endocrine (n = 2), or Sicca syndrome related (n = 2). grade 3 myocarditis and myositis (n = 1), grade 4 potentially attributable pneumonitis versus infectious reaction (n = 1) | 1CR,6SD,2PR, | 14 (95% CI, 5–17) | 1-year OS was 87% | |
2 | FAZ053 | 2SD | ||||||||||
1 | Nivolumab + bempegaldesleukin | PD | ||||||||||
2021 | phase2 | V | 34 | pembrolizumab 200mg |
The side effect profile of pembrolizumab was similar to other tumor type | 3PR | 6.6 | not reached | ||||
2022 | case report | V | 1 | clival | Surgery and radiotherapy | Pembrolizumab (200mg) | 3 | hypotension, severe fatigue, and dyspnea | ||||
2020 | case report | V | 1 | sacrum | surgery | pembrolizumab | grades 1–2, liver function and hyperglycemia | PR | 9.3 | |||
2017 | case report | V | 1 | spine | Surgery and radiotherapy | Pembrolizumab 200 mg | vitiligo | controlled for 6 months | ||||
1 | clival | Surgery and radiotherapy | Nivolumab 3 mg/kg | controlled for 9 months | ||||||||
2019 | case report | V | 1 | sacrum | radiotherapy | nivolumab, followed by nivolumab + ipilimumab | >4 | |||||
2017 | case series | IV | 2 | clival | radiotherapy | pazopanib + nivolumab | 161 | |||||
2021 | case report | V | 1 | clival | nivolumab | PR | ||||||
2021 | case report | V | 1 | sacrum | Surgery and radiotherapy | sintilimab + anlotinib | ICIs-related myocarditis | <1 | ||||
2017 | phase1 | V | 1 | avelumab (1,3,10,20mg/kg) | grade1/grade2 | |||||||
2019 | case series | IV | 1 | Durvalumab | Sicca/Sjögren’s syndrome | |||||||
2022 | phase2 | V | 5 | durvalumab + tremelimumab | Colitis, pneumonitis, abdominal pain, myocarditis | 1PR+CR,3SD,1PD | 13.57 (2.76, 17.81) |
Year | Study Design | Levels of Evidence | Sample Size | Tumor Site | Treatment History | Drug | Median Treatment Time (m) | AEs | Choi’s Criteria | RECIST/irRECIST | Median PFS (m) | Median OS (m) |
---|---|---|---|---|---|---|---|---|---|---|---|---|
22 | case series | IV | 5 | Durvalumab + tremelimumab | 12 | Colitis, pneumonitis, abdominal pain, myocarditis | 1PD,3SD,1PR | |||||
21 | phase1/2 | V | 1 | INT230-6 + ipilimumab | grade1/grade2, anemia, colitis | |||||||
19 | case report | V | 1 | sacrum | Radiotherapy | Nivolumab, followed by nivolumab + ipilimumab | >4 |
Year | Study Design | Levels of Evidence | Sample Size | Tumor Site | Treatment History | Drug | Median Treatment Time (m) | AEs | Choi’s Criteria | RECIST/irRECIST | Median PFS (m) | Median OS (m) |
---|---|---|---|---|---|---|---|---|---|---|---|---|
20 | phase1 | IV | 3 | MVA-brachyury s.c., 8 × 108 infectious units (IU), followed by FPV-brachyury s.c., 1 × 109 IU, | 24 | grade1/grade2, injection-site reaction, fever, fatigue | 2SD, 1PD | one patient for 52 weeks | ||||
20 | phase2 | III | 11 | 5 clival, 3 spine and 3 sacrum | GI-6301 (yeast-brachyury vaccine) +RT | injection-site reaction, lymphocyte count decreased, fever | 5PD,3SD,1 PR, | 20.6 | 37.5 | |||
21 | phase1 | IV | 10 | MVA-BN-brachyury-TRICOM vaccine (1 × 107, 1 × 108, 1 × 109) | grade1/grade2, injection-site reaction, fever | 4SD,5PD,1PR | 253 day | |||||
17 | phase1 | IV | 13 | MVA-brachyury-TRICOM (5 × 108, 1 × 109, 2 × 109) | grade1/grade2 (fever, diarrhea) injection-site reaction, lymphocyte count decreased, flu-like symptoms, fever, and diarrhea | |||||||
15 | phase1 | IV | 11 | 3 clival, 2 spine and 6 sacrum. | Surgery and radiotherapy | GI-6301 (yeast-brachyury vaccine) (4, 16, 40, and 80 yeast units (YU)) | grade1/grade2, injection-site reaction, fever | 3PD,1PR,1mixed response, 5SD | 8.3 |
Year | Study Design | Levels of Evidence | Sample Size | Tumor Site | Treatment History | Drug | Median Treatment Time (m) | AEs | Choi’s Criteria | RECIST/irRECIST | Median PFS (m) | Median OS(m) |
---|---|---|---|---|---|---|---|---|---|---|---|---|
2019 | phase1 | V | 5 | HuMax-IL8 (4, 8, 16, 32mg/kg) | 6 | constipation (33.3%), nausea (26.7%) and anemia (26.7%) | SD = 4, PD = 1 | 5.5 | ||||
2018 | phase1 | V | 1 | PG545 150mg | Hypertension, Chills, Fatigue | SD | ||||||
2021 | phase1 | V | 1 | C. novyi NT spores 1 × 106 | Pyrexia | SD | ||||||
2017 | case series | IV | 1 | clival | Surgery and radiotherapy | MVX-ONCO-1 | controlled >19 months | |||||
2017 | phase1 | V | 1 | clival | radiotherapy | HSV1716 (2 × 106 i.u.) | fever, chills, anemia and leukopenia | SD | 14day | 2.5 |
Clinical Trial | Trial registration Number | Phase | Medical Condition: | Sites | Status |
---|---|---|---|---|---|
Talimogene Laherparepvec, Nivolumab and Trabectedin for Sarcoma | NCT03886311 | 2 | Talimogene Laherparepvec, Nivolumab, Trabectedin | USA | Recruiting |
Nivolumab and Ipilimumab in Treating Patients With Rare Tumors | NCT02834013 | 2 | Ipilimumab, Nivolumab | USA | Recruiting |
Study of Nivolumab and Ipilimumab in Children and Young Adults With INI1-Negative Cancers | NCT04416568 | 2 | Ipilimumab, Nivolumab | USA | Recruiting |
Multi-Arm Study to Test the Efficacy of Immunotherapeutic Agents in Multiple Sarcoma Subtypes | NCT02815995 | 2 | Durvalumab, Tremelimumab | USA | Active, not recruiting |
A randomised, comparative, prospective, multicentre study of the efficacy of nivolumab + ipilimumab versus pazopanib alone in patients with metastatic or unresectable advanced sarcoma of rare subtype | EudraCT2020-002821-28 | 2 | nivolumab + ipilimumab versus pazopanib | France | Ongoing |
A randomized phase II study of Durvalumab (MEDI4736) and Tremelimumab compared to doxorubicin in patients with advanced or metastatic soft tissue sarcoma. | EudraCT 2016-004750-15 | 2 | Durvalumab (MEDI4736) and Tremelimumab compared to doxorubicin | Germany | Ongoing |
Multi-Arm Study to Test the Efficacy of Immunotherapeutic Agents in Multiple Sarcoma Subtypes | NCT02815995 | 2 | Durvalumab, Tremelimumab | USA | Active, not recruiting |
Nivolumab and Relatlimab in Treating Participants With Advanced Chordoma | NCT03623854 | 2 | Nivolumab, Relatlimab | USA | Recruiting |
Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors | NCT05286801 | 2 | Atezolizumab, Tiragolumab | USA | Recruiting |
Phase II trial of the immune checkpoint inhibitor nivolumab in patients with select rare CNS cancers | NCT03173950 | 2 | nivolumab | USA | Recruiting |
Phase I safety study of stereotactic radiosurgery with concurrent and adjuvant PD-1 antibody nivolumab in subjects with recurrent or advanced chordoma | NCT02989636 | 1 | nivolumab | USA | Recruiting |
TAEK-VAC-HerBy Vaccine for Brachyury and HER2 Expressing Cancer | NCT04246671 | 1 | TAEK-VAC-HerBy Vaccine | Recruiting | |
BN Brachyury and Radiation in Chordoma | NCT03595228 | 2 | BN-Brachyury plus radiation | ||
A Study of FAZ053 Single Agent and in Combination with PDR001 in Patients With Advanced Malignancies. | NCT02936102 | 1 | FAZ053 PDR001 | Completed Active, not recruiting | |
Nivolumab (Opdivo®) Plus ABI-009 (Nab-rapamycin) for Advanced Sarcoma and Certain Cancers | NCT03190174 | 2 | Nab-Rapamycin Nivolumab | Completed |
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Wang, X.; Chen, Z.; Li, B.; Fan, J.; Xu, W.; Xiao, J. Immunotherapy as a Promising Option for the Treatment of Advanced Chordoma: A Systemic Review. Cancers 2023, 15, 264. https://doi.org/10.3390/cancers15010264
Wang X, Chen Z, Li B, Fan J, Xu W, Xiao J. Immunotherapy as a Promising Option for the Treatment of Advanced Chordoma: A Systemic Review. Cancers. 2023; 15(1):264. https://doi.org/10.3390/cancers15010264
Chicago/Turabian StyleWang, Xiang, Zhaoyu Chen, Bo Li, Jiefu Fan, Wei Xu, and Jianru Xiao. 2023. "Immunotherapy as a Promising Option for the Treatment of Advanced Chordoma: A Systemic Review" Cancers 15, no. 1: 264. https://doi.org/10.3390/cancers15010264
APA StyleWang, X., Chen, Z., Li, B., Fan, J., Xu, W., & Xiao, J. (2023). Immunotherapy as a Promising Option for the Treatment of Advanced Chordoma: A Systemic Review. Cancers, 15(1), 264. https://doi.org/10.3390/cancers15010264