Abstract: No biomarkers are available to predict toxicities induced by VEGFR TKIs. This study aimed to identify markers of toxicities induced by these drugs using a discovery-validation approach. The discovery set included 140 sorafenib-treated cancer patients (TARGET study) genotyped for SNPs in 56 genes. The most significant SNPs associated with grade ≥2 hypertension, diarrhea, dermatologic toxicities, and composite toxicity (any one of the toxicities) were tested for association with grade ≥2 toxicity in a validation set of 201 sorafenib-treated patients (Alliance/CALGB 80802). The validated SNP was tested for association with grade ≥2 toxicity in 107 (LCCC 1029) and 82 (Italian cohort) regorafenib-treated patients. SNP-toxicity associations were evaluated using logistic regression, and a meta-analysis between the studies was performed by inverse variance. Variant rs4864950 in KDR increased the risk of grade ≥2 composite toxicity in TARGET, Alliance/CALGB 80802, and the Italian cohort (meta-analysis p = 6.79 × 10−4, OR = 2.01, 95% CI 1.34–3.01). We identified a predictor of toxicities induced by VEGFR TKIs. ClinicalTrials.gov Identifier:: NCT00073307 (TARGET), NCT01015833 (Alliance/CALGB 80802), and NCT01298570 (LCCC 1029).
KDR genetic predictor of toxicities induced by sorafenib and regorafenib / Quintanilha J.C.F., Geyer S., Etheridge A.S., Racioppi A., Hammond K., Crona D.J., Pena C.E., Jacobson S.B., Marmorino F., Rossini D., Cremolini C., Sanoff H.K., Abou-Alfa G.K., Innocenti F.. - In: PHARMACOGENOMICS JOURNAL. - ISSN 1470-269X. - ELETTRONICO. - 22:(2022), pp. 0-0. [10.1038/s41397-022-00279-3]
KDR genetic predictor of toxicities induced by sorafenib and regorafenib
Rossini D.;
2022
Abstract
Abstract: No biomarkers are available to predict toxicities induced by VEGFR TKIs. This study aimed to identify markers of toxicities induced by these drugs using a discovery-validation approach. The discovery set included 140 sorafenib-treated cancer patients (TARGET study) genotyped for SNPs in 56 genes. The most significant SNPs associated with grade ≥2 hypertension, diarrhea, dermatologic toxicities, and composite toxicity (any one of the toxicities) were tested for association with grade ≥2 toxicity in a validation set of 201 sorafenib-treated patients (Alliance/CALGB 80802). The validated SNP was tested for association with grade ≥2 toxicity in 107 (LCCC 1029) and 82 (Italian cohort) regorafenib-treated patients. SNP-toxicity associations were evaluated using logistic regression, and a meta-analysis between the studies was performed by inverse variance. Variant rs4864950 in KDR increased the risk of grade ≥2 composite toxicity in TARGET, Alliance/CALGB 80802, and the Italian cohort (meta-analysis p = 6.79 × 10−4, OR = 2.01, 95% CI 1.34–3.01). We identified a predictor of toxicities induced by VEGFR TKIs. ClinicalTrials.gov Identifier:: NCT00073307 (TARGET), NCT01015833 (Alliance/CALGB 80802), and NCT01298570 (LCCC 1029).
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