Table 5 The key reported clinical trials of of PD-1/PD-L inhibitors in patients with colorectal cancer
Tumor type | Target | Drug | Phase and identification | Sample size | Clinical end point | TRAEs | Reference |
|---|---|---|---|---|---|---|---|
CRC | PD-1 | Pembrolizumab + mFOLFOX6 | Phase II NCT02375672 | 30 | ORR 53%; SD 47%; 8-week DCR 100%; median PFS: not reached | Grades 3–4 36.7% (pembrolizumab + mFOLFOX6), 13.2% (pembrolizumab alone) | ASCO 2017 [161] |
CRC | PD-1 | Pembrolizumab | Electronic medical record | 19 | ORR 52%; CR 5%; PR 47%; SD 16%; DCR 68%; median OS 16.1Â months; 12-month OS rate 79%; median PFS not reached; 12-month PFS rate 54% | Data not available | ASCO 2017 [162] |
CRC | PD-1 | Nivolumab + ipilimumab | Phase II NCT02060188 | 27 | ORR 41%; SD 52%; DCR (≥12 weeks) 78%; medians for DOR, PFS and OS: not reached | Grades 3–4 37% | ASCO 2017 [163] |
CRC | PD-1 | Nivolumab | Phase II NCT02060188 | 74 | ORR 31% (INV), 27% (IRRC); DCR 69% (INV), 62% (IRRC); 12-month PFS rate 8.4% (INV), 45.6% (IRRC); median OS not reached; DOR not reached; 6-month OS rate 83.4%; 12-month OS rate 73.8% | Grades 3–4 20% | ASCO 2017 [69] |
CRC | PD-1 | Pembrolizumab | Phase II NCT01876511 | 53 | ORR 50% (dMMR), 0% (pMMR); DCR 89% (dMMR), 16% (pMMR); median PFS: not reached (dMMR); 2.4Â months (pMMR); median OS: not reached (dMMR); 6Â months (pMMR) | Data not available | ASCO 2016 [68] |
CRC | PD-L1 | Atezolizumab + cobimetinib | Phase I NCT01988896 | 23 | ORR 17% | Grades 3–4 34.8% | ASCO 2016 [70] |
CRC | PD-1 | Nivolumab; Nivolumab + Ipilimumab | Phase II NCT02060188 | 82 | ORR (MSI-H) 27% (nivolumab 3 mg/kg), 15% (nivolumab 3 mg/kg + ipilimumab 1 mg/kg); median PFS (MSI-H) 5.3 months (nivolumab 3 mg/kg), not reached (nivolumab 3 mg/kg + ipilimumab 1 mg/kg); median OS (MSI-H) 16.3 months (nivolumab 3 mg/kg), not reached (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) | Any grade (MSI-H): 79% (nivolumab 3 mg/kg), 85% (nivolumab 3 mg/kg + ipilimumab 1 mg/kg), including diarrhea and fatigue and diarrhea; Grades 3–4 (MSI-H) 21% (nivolumab 3 mg/kg), 31% (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) | ASCO 2016 [67] |
CRC | PD-1 | Pembrolizumab + radiotherapy/ablation | Phase II NCT02437071 | 19 | interim ORR 9% (pembrolizumab + radiotherapy), 0% (pembrolizumab + ablation) | Any grade 73%, including fatigue, rash, and nausea | ASCO 2016 [164] |
CRC | PD-1 | Pembrolizumab | Phase II NCT01876511 | 41 | ORR 40% (dMMR CRC), 0% (pMMR CRC), 71% (dMMR other cancers); DCR 90% (dMMR CRC), 11% (pMMR CRC), 71% (dMMR other cancers); median PFS: not reached (dMMR CRC); 2.2Â months (pMMR CRC); OS: not reached (dMMR CRC); 5.0Â months (pMMR CRC) | Data not available | ASCO 2015 [165] |