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)].

Gene

EGFR

Phenotype Category

Efficacy

Association Significance

The study reports this association is not significant

PharmGKB ID

1446908196

Evidence for Clinical Annotations

This annotation has been used as evidence for the following clinical annotations.

    Study Parameters

    1.

    Study type

    meta-analysis

    Study size

    709

    Association p-value

    = 0.08

    Statistical analysis

    HR: 0.49

    Confidence interval

    0.22 - 1.09

    Population description

    men; women

    Drug: afatinib vs chemotherapy on PFS; I squared value= 82.0%

    2.

    Study type

    meta-analysis

    Study size

    709

    Statistical analysis

    HR: 1.12

    Confidence interval

    0.94 - 1.34

    Population description

    men; women

    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.

    History

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