Table 1.
Clinical trials investigating the benefit of immune checkpoint inhibitors in MMR-D/MSI-H CRC patients
| Study | Le et al.10 | Overman et al.9 | Overman et al.12 |
|---|---|---|---|
| Design | Phase 2 | Phase 2 | Phase 2 |
| Number of CRC patients enrolled in the study | A total of 41 patients with various cancer including 10 with metastatic MMR-D/MSI-H CRC | 74 metastatic MMR-D/MSI-H CRC patients | 119 metastatic MMR-D/MSI-H CRC patients |
| Agent | Pembrolizumab | Nivolumab | Nivolumab and ipilimumab |
| Dose | 10 mg/kg every 2 weeks | 3 mg/kg every 2 weeks | Nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg every 3 weeks ×4 followed by nivolumab 3 mg/kg every 2 weeks |
| ORR | 40% | 31% | 55% |
| PFS | PFS rate at ~5 months (20 weeks) was 78% | PFS rate at 12 months was 50% | PFS rates at 9 months and 12 months were 76% and 71%, respectively |
| Common adverse effects | Fatigue (32%), rash (24%), diarrhoea (24%), pancreatitis (15%) | Fatigue (23%), diarrhoea (22%), pruritus (10%), rash (10%) | Diarrhoea (22%), fatigue (18%), pruritus (17%), rash (11%), hypothyroidism (14%) |
| Biomarkers investigated | CD8 and PD-L1 expressions were not predictors of outcome | BRAF, KRAS mutations, PD-L1 expression and Lynch syndrome were not predictors of response | BRAF, KRAS mutations, PD-L1 expression and Lynch syndrome were not a predictor of response |
CRC Colorectal cancer, MMR-D Mismatch repair deficiency, MSI-H Microsatellite instability high, ORR Overall response rate, PFS Progression-free survival, PD-L1 Programmed death-ligand 1