Annotation of rs121434568
Allele G is not associated with response to afatinib in people with Carcinoma, Non-Small-Cell Lung.
as first line agents and as compared to chemotherapy. These results are for a meta-analysis of clinical trials (LUXLUNG6, LUXLUNG3). A random effects model was used to compile the results since there was heterogeneity across the trials. Progression free and overall survival (PFS, OS) were the measures of response. As compared to standard chemotherapy, patients with this SNP had increased PFS, but not OS when taking afatinib. Overall, however, a different EGFR mutation, "exon 19 del", had a greater improvement in response to tyrosine kinase inhibitors (TKIs) as compared to chemotherapy than the rs121434568 T>G mutation [(PFS "exon 19 del"/rs121434568 T>G HR 0.58 (95% CI 0.45-0.75); p-value= 0.001) and OS "exon 19 del"/rs121434568 T>G HR 0.75 (95% CI 0.58-0.94)' p-value=0.018)].
From Publication
Gene
Variant
Phenotype Category
Association Significance
PharmGKB ID
Score More info on scoring
Evidence for Clinical Annotations
This annotation has been used as evidence for the following clinical annotations.
Study Parameters
1.
Study type
Study size
Association p-value
Statistical analysis
Confidence interval
Population description
Drug: afatinib vs chemotherapy on PFS; I squared value= 82.0%
2.
Study type
Study size
Statistical analysis
Confidence interval
Population description
Drug: afatinib vs chemotherapy on OS; I squared value= 0.0%
Note: Alleles in PharmGKB are mapped to the positive chromosomal strand. Therefore, variants in genes on the "minus" strand (eg. VKORC1) are complemented in PharmGKB annotations.