Table 1. Outcomes of RAS Mutations and Anti-EGFR Therapy
Overall Survival Progression-Free Survival
Characteristic HR (95% CI) p Value HR (95% CI) p Value
RAS nm v RAS
mutation, RAS nm
superior
0.72 (0.56 to 0.92) <.01 0.6 (0.48 to 0.76) <0.001
KRAS exon 2 mutant v
new RAS mutant
ns ns
KRAS nm exon 2, anti-
EGFR v no anti-EGFR
0.9 (0.83 to 0.98) ns 0.68 (0.58 to 0.80) <0.001
KRAS exon 2 mutant,
anti-EGFR v no anti-
EGFR
1.05 (0.95 to 1.17) ns 1.14 (0.95 to 1.36) ns
RAS nm, anti-EGFR v no
anti-EGFR
0.87 (0.77 to 0.99) <0.04 0.62 (0.5 to 0.76) <0.001
Any RAS mutant, anti-
EGFR v no anti-EGFR
1.08 (0.97 to 1.21) ns 1.12 (0.94 to 1.34) ns
Table 2. Concordance Rates Between Primary and Metastatic
Lesions
a
Genes Tested (n) Concordance Rate (%)
KRAS (117) 91
KRAS, NRAS, BRAF (84) 98.8
PIK3CA (117) 94
PIK3CA (84) 92.8
PTEN immunohistochemistry 66
a
Summary of two randomized clinical trials where comparison of mutation in KRAS, NRAS, BRAF,
and PIK3CA was performed for paired primary tumor and metastatic lesions. Immunohistochemistry
for PTEN was done in Cejas et al. (Curr Cancer Drug Targets 12:124-131, 2012). In the study by
Cejas et al. metastases were synchronous or metachronous. DNA was extracted from formalin-fixed,
paraffin-embedded tissue, and mutational analysis was performed with a polymerase chain reaction–
direct sequencing assay. KRAS mutations were detected in 42% of metastatic lesions and 39% of
primary tumors. In the study by Vakiani et al. (J Clin Oncol. 30:2956-2962, 2012) DNA was extracted
from frozen tissue, and the iPLEX assay (Agena Bioscience, San Diego, CA) was used to examine
the following mutations: KRAS 12, 13, 22, 61, 117, and 146; NRAS 12, 13, and 61; BRAF 600; and
PIK3CA 345, 420, 542, 545, 546, 1043, and 1047.
