Table 1.
Selected past and ongoing prospective clinical trials on anti-EGFR re-challenge in metastatic CRC.
| Trial | Phase | Sample size | Treatment arm(s) | Previous treatments | ORR (%) | mPFS (months) | mOS (months) | Remarks |
|---|---|---|---|---|---|---|---|---|
| CRICKET38 | II | 28 | Cetuximab + irinotecan | 1L cetuximab + irinotecan-based chemotherapy; 2L bevacizumab + oxaliplatin-based chemotherapy | 21 | 3.4 | 9.8 | ctDNA RAS-wt patients had prolonged mPFS (4.0 versus 1.9 months) |
| E-RECHALLENGE39 | II | 33 | Cetuximab + irinotecan | Fluoropyrimidine, oxaliplatin, irinotecan, cetuximab and bevacizumab | 15.6 | 2.9 | 8.6 | ctDNA RAS-wt patients had prolonged mPFS (7.0 versus 2.9 months) |
| JACCRO CC-0840 | II | 34 | Cetuximab + irinotecan | 1L cetuximab + irinotecan/oxaliplatin-based chemotherapy; 2L oxaliplatin/irinotecan-based chemotherapy | 2.9 | 2.4 | 8.2 | Patients with anti-EGFR-free interval >372 days had prolonged mPFS (4.6 versus 2.1 months) and mOS (14.1 versus 6.3 months) |
| JACCRO CC-0941 | II | 25 | Panitumumab + irinotecan | 1L panitumumab + FOLFOX/FOLFIRI; 2L bevacizumab/panitumumab + chemotherapy | 8.3 | 3.1 | 8.9 | Patients with anti-EGFR-free interval >372 days had prolonged mPFS (4.42 versus 2.51 months) and mOS (15.84 versus 7.33 months) |
| CHRONOS42 | II | 27 | Panitumumab | Previous anti-EGFR in 1L (63%), 2L (15%) or >2L (22%) | 30 | 3.7 | – | Only patients with ctDNA RAS/BRAF/EGFR-wt were enrolled |
| CAVE43 | II | 77 | Cetuximab + avelumab | 1L anti-EGFR + chemotherapy, at least one >1L therapy | 7.8 | 3.6 | 11.6 | ctDNA RAS/BRAF-wt patients had prolonged mPFS (4.1 versus 3.0 months) and mOS (17.3 versus 10.4 months); 4% were MSI-high tumours |
| REMARRY & PURSUIT45 (UMIN000036424) (jRCTs031190096) | II | 50 | Panitumumab + irinotecan | Fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR | 14 | 3.6 | – | ctDNA RAS-wt patients had better ORR (16% versus 0%); patients with anti-EGFR-free interval >365 days had better ORR (44.4% versus 7.3%) |
| FIRE-4 (NCT02934529) | III | 550 | Cetuximab + irinotecan-based chemotherapy versus regorafenib | 1L cetuximab + FOLFIRI; 2L bevacizumab + FOLFOX | – | – | – | – |
| CAPRI II GOIM (NCT05312398) | II | 200 | Cetuximab + irinotecan versus TAS-102 or regorafenib | 1L cetuximab + FOLFIRI; 2L cetuximab + FOLFOX versus bevacizumab + FOLFOX | – | – | – | Patients will be selected for suitable second- and third-line therapies according to ctDNA RAS-BRAF status |
| PULSE (NCT03992456) | II | 120 | Panitumumab versus TAS-102 or regorafenib | – | – | – | – | ctDNA analysis included |
| PARERE (NCT04787341) | II | 214 | Panitumumab followed by regorafenib versus regorafenib followed by panitumumab | 1L anti-EGFR-based therapy; previous 5-FU, oxaliplatin, irinotecan and anti-angiogenics | – | – | – | Only ctDNA RAS/BRAF-wt patients will be enrolled |
| VELO (EudraCT: 2018-001600-12) | II | 112 | Panitumumab + TAS-102 versus TAS-102 alone | – | – | – | – | – |
| NCT03524820 | II | 60 | Cetuximab ± chemotherapy | 1L anti-EGFR + chemotherapy; other 2L treatments | – | – | – | – |
ctDNA, circulating tumour DNA; EGFR, epidermal growth factor receptor; mOS, median overall survival; mPFS, median progression-free survival; MSI, microsatellite instability; ORR, objective response rate; wt, wild type; 1L, first-line therapy; 2L, second-line therapy; 5-FL, 5-fluorouracil.