Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer
Abstract
:1. Introduction
2. Local Treatment
2.1. Surgery
2.2. Whole Brain Radiotherapy
2.3. Stereotactic Radiosurgery and Stereotactic Radiotherapy
2.4. Exploration of New Local Treatment Methods
3. Chemotherapy
4. Targeted Therapy
4.1. Targeted Therapy with EGFR Tyrosine Kinase Inhibitors
4.2. Targeted Therapy with ALK-TKI
4.3. Other Targeted Therapies
5. Immunotherapy
5.1. Treatment Progress of ICI Monotherapy in NSCLC CNS Metastasis
5.2. Treatment Progress of ICI Monotherapy Combined with Chemotherapy/Radiotherapy for NSCLC CNS Metastasis
6. Discussion
6.1. Choice of Clinical Treatment Model for NSCLC CNS Metastasis with Driver Mutations
6.2. Prognostic Factors of NSCLC CNS Metastasis
7. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Clinical Trials/NCT Numbers | Drugs | Phase | Sample Size | OS (Months) | Ref |
---|---|---|---|---|---|
KEYNOTE-001/NCT01295827 | Pembrolizumab | I | 1260 | 12 | [107] |
KEYNOTE-010/NCT01905657 | Pembrolizumab | II–III | 1034 | 11.8 | [108] |
IND-121564/NCT02085070 | Pembrolizumab | II | 65 | 7.7 | [109] |
KEYNOTE-021/NCT02039674 | Pembrolizumab | I–II | 267 | 16.7 | [110] |
Pembrolizumab combined with carboplatin and paclitaxel | 21.4 | ||||
Pembrolizumab combined with carboplatin, paclitaxel, and bevacizumab | 16.7 | ||||
Pembrolizumab combined with carboplatin and pemetrexed | 16.7 | ||||
KEYNOTE-024/NCT02142738 | Pembrolizumab | III | 305 | 30 | [111] |
KEYNOTE-028/NCT02054806 | Pembrolizumab | I | 477 | 11.3 | [112] |
CheckMate-017/NCT01642004 | Nivolumab | III | 352 | 9.2 | [113] |
CheckMate-057/NCT01673867 | Nivolumab | III | 792 | 12.2 | [114] |
CheckMate-063/NCT01721759 | Nivolumab | II | 140 | 8.2 | [115] |
CheckMate-227/NCT02477826 | Nivolumab plus ipilimumab | III | 2220 | 17.1 | [116] |
CheckMate-012/NCT01454102 | Nivolumab plus erlotinib | I | 472 | 19.2 | [117,118,119] |
Nivolumab | 19.4 | ||||
FIR/NCT01846416 | Atezolizumab | II | 138 | 6.3 | [120] |
OAK/NCT02008227 | Atezolizumab | III | 1225 | 13.8 | [121] |
POPLAR/NCT01903993 | Atezolizumab | III | 287 | 12.6 | [122] |
IMpower150/NCT02366143 | Atezolizumab combined with carboplatin and paclitaxel | III | 1202 | 14.4 | [123] |
Atezolizumab combined with bevacizumab, carboplatin, and paclitaxel | 19.2 | ||||
IMPower-131/NCT02367794 | Atezolizumab combined with carboplatin and paclitaxel | III | 1021 | 14 | [124] |
PACIFIC/NCT02125461 | Durvalumab | III | 713 | 28.3 | [125] |
Study 1108/NCT01693562 | Durvalumab | I-II | 1022 | 12.4 | [126] |
ATLANTIC/NCT02087423 | Durvalumab | II | 446 | 13.2 | [127] |
CAURAL/NCT02454933 | Durvalumab and osimertinib | III | 29 | Not reported | [128] |
TATTON/NCT02143466 | Durvalumab and osimertinib | I | 344 | Not reported | [129] |
NCT02000947 | Durvalumab and tremelimumab | I | 459 | Not reported | [130] |
ARCTIC/NCT02352948 | Durvalumab | II | 597 | 11.7 | [131] |
Durvalumab and tremelimumab | 11.5 | ||||
IND226/NCT02537418 | Durvalumab | I | 153 | 19.8 | [132] |
Drug Name | Cerebrospinal Fluid Concentration | Cerebrospinal Penetration Rate | Ref |
---|---|---|---|
EGFR-targeted therapies | |||
Erlotinib | 28.7 ng/mL (66.9 nM) | 2.8–3.3% | [145,146] |
Gefitinib | 3.7 ng/mL (8.2 nM) | 1.13% | [145] |
Afatinib | 1.4 ng/mL (2.9 nM); 1 nM | 1.65% | [147] |
Osimertinib | 7.51 nM | 2.5–16% | [148,149] |
AZD3759 | 25.2 nM | 100% | [150] |
ALK-targeted therapies | |||
Crizotinib | 0.616 ng/mL (0.14 nM) | 0.26% | [84] |
Ceritinib | No data | 15% | [151,152] |
Alectinib | 2.69 nM | 63–94% | [153,154] |
Lorlatinib | 2.64–125 ng/mL (6.5–308 nM) | 20–96% | [95,152,155] |
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Wang, B.; Guo, H.; Xu, H.; Yu, H.; Chen, Y.; Zhao, G. Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer. Cells 2021, 10, 2620. https://doi.org/10.3390/cells10102620
Wang B, Guo H, Xu H, Yu H, Chen Y, Zhao G. Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer. Cells. 2021; 10(10):2620. https://doi.org/10.3390/cells10102620
Chicago/Turabian StyleWang, Bin, Hanfei Guo, Haiyang Xu, Hongquan Yu, Yong Chen, and Gang Zhao. 2021. "Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer" Cells 10, no. 10: 2620. https://doi.org/10.3390/cells10102620
APA StyleWang, B., Guo, H., Xu, H., Yu, H., Chen, Y., & Zhao, G. (2021). Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer. Cells, 10(10), 2620. https://doi.org/10.3390/cells10102620