Table 1.
Summary of rechallenge/reintroduction trials with anti-EGFR agents.
| Study | Design | N | Patient population | Site (n) | Line | RR, % | SD, % | DCR, % | PFS, months | OS, months | Common grade 3/4 AEs, % |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Santini et al. 2012 (19) | Phase II | 39 |
KRAS codons 12–13 wt |
Colon (19); rectum/rectosigmoid (20) | ≥4 | 53.8 | 35.9 | 89.8 | 6.6 | NR | Skin rash (38.5), neutropenia (18.0), diarrhea (7.7) |
| JACCRO CC-08 (47) | Phase II | 34 | KRAS wt | Right colon (4), left colorectum (30) | 3 | 2.9 | 53.0 | 55.9 | 2.4 | 8.2 | Neutropenia (28.6) |
| JACCRO CC-09 (48) | Phase II | 25 |
KRAS wt exon 2 |
NR | 3 | 8.3 | 41.7 | 50 | 3.1 | 8.9 | Acneiform rash (17), hypomagnesemia (13) and dry skin (13) |
| Nogueira et al., 2016 (49) | Retrospective | 15 | KRAS wt | Colon (10); rectum (5) | ≥3 | 13.3* | 26.7 | 40.0 | 3.5 | 36.9 | Skin toxicity (13.3) |
| Tanioka et al., 2018 (50) | Retrospective | 14 |
KRAS wt exon 2 |
NR | 3–6 | 21.4 | 50.0 | 71.4 | 4.4 | NR | Rash (7), diarrhea (7) |
| E-Rechallenge (21) | Phase II | 33 | RAS wt | Right colon (4); left colon (29) |
NS | 15.6* | 40.6 | 56.2 | 2.9 | 8.7 | NR |
| CRICKET (20) | Phase II | 28 | RAS/BRAF wt | Right colon (9); left colon or rectum (19) | 3 | 21 | 31 | 54 | RAS wt: 4.0 | RAS wt: 12.5 | Diarrhea (18), acneiform skin rash (14), neutropenia (14), hand and foot syndrome (7) |
| E-Rechallenge (additional study) (22) | Phase II | 24 | RAS wt | NR | NS | 12.5* | 50.0 | 62.5 | NR | NR | NR |
| TRECC (51) | Retrospective | 68 | KRAS/NRAS wt | Right/ transverse colon (4); left/rectum (64) |
≥3 | 18 | NR | NR | 3.3 | 7.5 | NR |
| CAVE (52) | Phase II | 77 | RAS wt | NR | 3 | 7.8 | 57.1 | 65 | 3.6 | 11.6 | Cutaneous eruption (14), diarrhea (4) |
| CHRONOS (23) | Phase II | 27 | RAS/BRAF wt | Right colon (5); left colon (17); rectum (5) | ≥4 | 30* | 40 | 63 | 16 weeks | 55 weeks | Dermatological (22) |
| PURSUIT (53) | Phase II | 50 | RAS/BRAF wt | Left-sided primary (44) | ≥2 | 14 | 66 | 80 | 3.6 | NR | NR |
In the TRECC study, only 25% of patients were rechallenged with an anti-EGFR agent and 75% were reintroduced to an anti-EGFR agent. *Partial response.
AE, adverse event; DCR, disease control rate; EGFR, epidermal growth factor receptor; NR, not reported; NS, not specified; OS, overall survival; PFS, progression-free survival; RR, relative risk; SD, stable disease; wt, wild-type.