Table 2.
The relationship between ICB and dMMR/MSI-H
| Author/year | Cancer type | N | Protocol | Results | PFS | OS |
|---|---|---|---|---|---|---|
|
Le DT [65] 2015 |
dMMR CRC | 41 | Pembrolizumab 10 mg/kg, q14d, 20 weeks | ORR 40% | 20-week PFS, 78%; mPFS: NR | mOS: NR |
| pMMR CRC | ORR 0% | 20-week PFS, 11%; mPFS: 2.2 months | mOS, 5.0 months | |||
| dMMR non-CRC | ORR 71% | 20-week PFS, 67%; mPFS: 5.4 months | mOS: NR | |||
| pMMR CRC | 25 |
ORR 0% DCR16% |
mPFS, 2.4 months | mOS, 6 months | ||
|
Le DT [30] 2017 |
12 tumors with dMMR | 86 | Pembrolizumab 10 mg/kg, q14d, 2 years |
ORR 53% DCR 66% |
12-month PFS, 64% 24-month PFS, 53%;mPFS: NR |
12-month OS, 76% 24-month OS, 64%;mOS: NR |
|
Diaz LA [66] 2017 |
Multiple types of solid tumors | 77 | Pembrolizumab 200 mg, q3w, 35 cycles |
ORR 38% DCR 58% |
6-month PFS, 45% mPFS, 4.3 months |
6-month OS, 73%;mOS: NR |
|
D Le [67] 2018 |
MMR/dMMR CRC | 63 | Pembrolizumab 200 mg, q3w, 35 cycles |
ORR 28% DCR 51% |
6-month PFS, 43% 12-month PFS, 41%;mPFS, 4.1 months |
6-month OS, 87% 12-month OS, 76%;mOS: NR |
|
Overman MJ [68] 2017 |
dMMR/MSI-H mCRC | 74 | Nivolumab 3 mg/kg, q2w, until PD |
ORR 31% DCR 69% (≥ 12 weeks) |
12-month PFS, 50% mPFS, 14.3 months |
12-month OS, 73%;mOS: NR |
|
Overman MJ [71] 2018 |
dMMR/MSI-H mCRC | 119 | Nivolumab 3 mg/kg + ipilimumab 1 mg/kg, q3w, 4 doses, followed by nivolumab 3 mg/kg, q2w, until PD |
ORR 55% DCR 80% |
9-month PFS, 76% 12-month PFS, 71%;mPFS: NR |
9-month OS, 87% 12-month OS, 85%;mOS: NR |
|
H-J J Lenz [72] 2018 |
dMMR/MSI-H mCRC | 45 | Nivolumab 3 mg/kg, q2w + ipilimumab 1 mg/kg, q6w, until PD (as first-line treatment) |
ORR 60% DCR 84% |
12-month PFS, 78%;mPFS: NR | 12-month OS: 83%;mOS: NR |
|
M Chalabi [73] 2018 |
dMMR early-stage CC pMMR early-stage CC |
7 8 |
Nivolumab 3 mg/kg, d1, d15 + ipilimumab 1 mg/kg, d1 |
mPR 100% mPR 0% |
NA | NA |
Abbreviations: dMMR mismatch repair deficient, CRC colorectal cancer, mCRC metastatic colorectal cancer, CC colon cancers, pMMR mismatch repair proficient, ORR objective response rate, PFS progression-free survival, mPFS median progression-free survival, NR not reached (the responses were durable and the results were not reached until the end of follow-up), mOS median overall survival, DCR disease control rate, OS overall survival, mCRC metastatic colorectal cancer, MSI-H microsatellite instability-high, PD disease progression, mPR major pathological response, NA not available