Table 2.
Trials assessing downstream mutations in the EGFR pathway and resistance to the EGFR monoclonal antibodies.
| Trial | Patient Number |
Wt KRAS (%) Responders (%) |
Mt KRAS (%) | BRAF mutation Association | PTEN loss of expression Association | PIK3CA mutation Association | Other |
|---|---|---|---|---|---|---|---|
| Lievre et al. | 30 | 17 (63%) Res 11/17 (65%) |
13 (43%) | 0 | na | 2 (7%) [in KRAS mt pts] | EGFR copy number (3 pts-10%) correlates with response |
| Di Nicolantonio et al. | 113 | 79 (70%) Res 22/79 (28%) |
34 (30%) | 11/79 (10%) Shorter PFS (p = 0.011) and OS (p < 0.0001) | na | na | Sorafenib restored sensitivity to EGFR mabs in pts with BRAF MT |
| Laurent-Puig et al | 169 | 116 (69%) Res 52/116 (45%) |
53 (31%) | 5/116 (2.9%) Lower RR (p = 0.63), PFS and OS (p < 0.001) | 22/116 (19.8%) Shorter OS (p = 0.013) | na | High EGFR polysomy in 17.7% and correlates with response |
| Loupakis et al. | 122 (88 KRAS, 85 PTEN) | 53 Res 13/53 (25%) |
35/88 (40%) Concordance 95% | na | 49/85 (58%) Concordance 60% Higher RR/PFS with KRAS wt/PTEN + mets (p = 0.0004, p = 0.001) | na | pAKT-positive 35/96 (40%) Concordance 68% |
| Sartore-Bianchi et al. | 132 | 43 Res 22/43 (51%) |
35 (26.5%) | 11 (8.3%) Shorter OS | 41 (36%) Lower RR and OS | 15 (12.3%) More common in exon 20 Lower RR | KRAS and BRAF mutually exclusive only |
Res = responders; na = not assessed; NR = non-responder; Wt = wild type; mt = mutant; RR = response rate; PFS = progression free survival; OS = overall survival; mabs = monoclonal antibodies; Concordance = concordance between primary tumor and metastases.