Journal of Shanghai Jiao Tong University (Medical Science) ›› 2023, Vol. 43 ›› Issue (2): 250-255.doi: 10.3969/j.issn.1674-8115.2023.02.016
• Review • Previous Articles
Received:
2022-05-20
Accepted:
2022-10-27
Online:
2023-02-28
Published:
2023-02-28
Contact:
JIN Zhiming
E-mail:1093673466@qq.com;jzmgyp@hotmail.com
Supported by:
CLC Number:
TU Juanjuan, JIN Zhiming. Research progress of immune checkpoint inhibitors in the treatment of metastatic colorectal cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(2): 250-255.
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URL: https://xuebao.shsmu.edu.cn/EN/10.3969/j.issn.1674-8115.2023.02.016
Trial (stage) | Target population | Regimen (total) | Key-outcome | TRAE of grade≥3 |
---|---|---|---|---|
NCT03274804[ | MSS/pMMR mCRC | Pembrolizumab+maraviroc (20) | ORR: 5.3%; mPFS: 2.10 months; mOS: 9.83 months | 5% (hyperglycemia) |
NCT02407990[ | Advanced CRC | Tislelizumab (21) | ORR: 14.3% | ‒ |
NCT03712943[ | Refractory, MSS/pMMR mCRC | Nivolumab+regorafenib (51) | mPFS: 4.3 months; mOS: 11.1 months | 51% (hypertension 16%, rash 10% and lymphopenia 8%) |
CheckMate142[ | First-line treatment intolerance or disease progression, MSI-H/dMMR mCRC | Nivolumab (74) | ORR: 31.1%; PFS rate: 50%; OS rate: 73% (median follow-up was 60.9 months); DDC≥12 weeks: 69% | 20% (lipase elevation 8%, amylase elevation 3%) |
NCT03150706[ | Age≥20 years, failure of first-line chemotherapy, MSI-H/dMMR or POLE-mutated mCRC | Avelumab (33) | ORR: 28.6%; DCR: 90.5%; mPFS: 3.9 months; mOS: 13.2 months | 18.20% |
NCT02873195[ | Disease progression, 89.4% were MSS/pMMR mCRC | Capecitabine+bevacizumab+atezolizumab (87) vs capecitabine+bevacizumab+placebo (46) | mPFS: 4.4 vs 3.6 months; mOS: 10.2 vs 10.3 months | 61.6% vs 58.7% (skeptical) |
NCT03186326[ | Age 18‒75 years, failure of first-line therapy, MSI-H/dMMR mCRC | Avelumab vs second-line theray±targeted therapy | Ongoing | ‒ |
NCT04561336[ | Chemotherapy-refractory, wild-type RAS, 92.2% were MSS/pMMR mCRC | Avelumab+cetuximab (77) | mPFS: 3.6 months; mOS: 11.6 months | Rash 14% and diarrhea 4% included |
NCT03608046[ | Wild-type BRAFV600E, MSS/pMMR mCRC | Avelumab+cetuximab+irinotecan (10) | mPFS: 4.2 months; mOS: 12.7 months | 0 |
CheckMate142[ | MSI-H/dMMR mCRC | Nivolumab+low-dose ipilimumab (45) | OS rate at 12, 18 and 24 months were 84.1%, 81.7% and 79.4%; PFS rate at 12, 18 and 24 months were 76.4%, 76.4% and 73.6% | 22% (colitis 4%, respiratory failure 2%) |
NCT02870920[ | Refractory CRC | Durvalumab+tremelimumab (118) vs best supportive care (61) | mPFS: 1.8 vs 1.9 months; mOS: 6.6 vs 4.1 months | 62% vs 20% |
NCT03122509[ | Chemotherapy-refractory, MSS/pMMR mCRC | Durvalumab+tremelimumab+radiotherapy (24) | ORR: 8.3%; mPFS: 1.8 months; mOS: 11.4 months (median follow-up was 21.8 months) | 25% (diarrhea 13%, colitis 8% and hyperglycemia 8%) |
KEYNOTE-177[ (NCT02563002)(Ⅲ) | MSI-H/dMMR mCRC | Pembrolizumab (153) vs mFOLFOX6 or FOLFIRI (±bevacizumab/cetuximab) (154) | mPFS: 16.5 months; mOS: 8.2 months | 22% (colitis 3%, hepatitis 3%) vs 66% |
IMblaze370[ | Have received other treatments | Atezolizumab+cobimetinib (183) vs atezolizumab (90) vs regorafenib (90) | mOS: 8.87 vs 7.10 vs 8.51 months | 61% vs 31% vs 58% |
Tab 1 Summary of recent clinical trials of ICI therapy in adult patients with mCRC
Trial (stage) | Target population | Regimen (total) | Key-outcome | TRAE of grade≥3 |
---|---|---|---|---|
NCT03274804[ | MSS/pMMR mCRC | Pembrolizumab+maraviroc (20) | ORR: 5.3%; mPFS: 2.10 months; mOS: 9.83 months | 5% (hyperglycemia) |
NCT02407990[ | Advanced CRC | Tislelizumab (21) | ORR: 14.3% | ‒ |
NCT03712943[ | Refractory, MSS/pMMR mCRC | Nivolumab+regorafenib (51) | mPFS: 4.3 months; mOS: 11.1 months | 51% (hypertension 16%, rash 10% and lymphopenia 8%) |
CheckMate142[ | First-line treatment intolerance or disease progression, MSI-H/dMMR mCRC | Nivolumab (74) | ORR: 31.1%; PFS rate: 50%; OS rate: 73% (median follow-up was 60.9 months); DDC≥12 weeks: 69% | 20% (lipase elevation 8%, amylase elevation 3%) |
NCT03150706[ | Age≥20 years, failure of first-line chemotherapy, MSI-H/dMMR or POLE-mutated mCRC | Avelumab (33) | ORR: 28.6%; DCR: 90.5%; mPFS: 3.9 months; mOS: 13.2 months | 18.20% |
NCT02873195[ | Disease progression, 89.4% were MSS/pMMR mCRC | Capecitabine+bevacizumab+atezolizumab (87) vs capecitabine+bevacizumab+placebo (46) | mPFS: 4.4 vs 3.6 months; mOS: 10.2 vs 10.3 months | 61.6% vs 58.7% (skeptical) |
NCT03186326[ | Age 18‒75 years, failure of first-line therapy, MSI-H/dMMR mCRC | Avelumab vs second-line theray±targeted therapy | Ongoing | ‒ |
NCT04561336[ | Chemotherapy-refractory, wild-type RAS, 92.2% were MSS/pMMR mCRC | Avelumab+cetuximab (77) | mPFS: 3.6 months; mOS: 11.6 months | Rash 14% and diarrhea 4% included |
NCT03608046[ | Wild-type BRAFV600E, MSS/pMMR mCRC | Avelumab+cetuximab+irinotecan (10) | mPFS: 4.2 months; mOS: 12.7 months | 0 |
CheckMate142[ | MSI-H/dMMR mCRC | Nivolumab+low-dose ipilimumab (45) | OS rate at 12, 18 and 24 months were 84.1%, 81.7% and 79.4%; PFS rate at 12, 18 and 24 months were 76.4%, 76.4% and 73.6% | 22% (colitis 4%, respiratory failure 2%) |
NCT02870920[ | Refractory CRC | Durvalumab+tremelimumab (118) vs best supportive care (61) | mPFS: 1.8 vs 1.9 months; mOS: 6.6 vs 4.1 months | 62% vs 20% |
NCT03122509[ | Chemotherapy-refractory, MSS/pMMR mCRC | Durvalumab+tremelimumab+radiotherapy (24) | ORR: 8.3%; mPFS: 1.8 months; mOS: 11.4 months (median follow-up was 21.8 months) | 25% (diarrhea 13%, colitis 8% and hyperglycemia 8%) |
KEYNOTE-177[ (NCT02563002)(Ⅲ) | MSI-H/dMMR mCRC | Pembrolizumab (153) vs mFOLFOX6 or FOLFIRI (±bevacizumab/cetuximab) (154) | mPFS: 16.5 months; mOS: 8.2 months | 22% (colitis 3%, hepatitis 3%) vs 66% |
IMblaze370[ | Have received other treatments | Atezolizumab+cobimetinib (183) vs atezolizumab (90) vs regorafenib (90) | mOS: 8.87 vs 7.10 vs 8.51 months | 61% vs 31% vs 58% |
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