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IL8 polymorphisms and overall survival in pazopanib- or sunitinib-treated patients with renal cell carcinoma.

Xu CF, Johnson T, Garcia-Donas J, Choueiri TK, Sternberg CN, Davis ID, Bing N, Deen KC, Xue Z, McCann L, Esteban E, Whittaker JC, Spraggs CF, Rodríguez-Antona C, Pandite LN, Motzer RJ - Br. J. Cancer (2015)

Bottom Line: In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8 × 10(-5); variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15-1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients.Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC.These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies.

View Article: PubMed Central - PubMed

Affiliation: GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.

ABSTRACT

Background: We evaluated germline single nucleotide polymorphisms (SNPs) for association with overall survival (OS) in pazopanib- or sunitinib-treated patients with advanced renal cell carcinoma (aRCC).

Methods: The discovery analysis tested 27 SNPs within 13 genes from a phase III pazopanib trial (N=241, study 1). Suggestive associations were then pursued in two independent datasets: a phase III trial (COMPARZ) comparing pazopanib vs sunitinib (N=729, study 2) and an observational study of sunitinib-treated patients (N=89, study 3).

Results: In study 1, four SNPs showed nominally significant association (P≤0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated (P≤0.05) with OS in study 2. Because rs1126647 and rs4073 were highly correlated, only rs1126647 was evaluated in study 3, which also showed association (P≤0.05). In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8 × 10(-5); variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15-1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients.

Conclusions: Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC. These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies.

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Related in: MedlinePlus

Forest plot of meta-analysis association results between IL8 rs1126647 polymorphism and OS across three independent studies (with confirmation study 2 split into pazopanib- and sunitinib-treated subgroups). The HR was per variant T allele compared with reference A allele using an additive genetic model.
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fig2: Forest plot of meta-analysis association results between IL8 rs1126647 polymorphism and OS across three independent studies (with confirmation study 2 split into pazopanib- and sunitinib-treated subgroups). The HR was per variant T allele compared with reference A allele using an additive genetic model.

Mentions: In study 1 (pazopanib-treated, N=241), rs1126647 was significantly associated with OS (N=186; 125 events; P=0.007, per allele HR=1.45, 95% confidence interval (CI): 1.11–1.91; 18 patients had missing genotype data and 37 patients had missing data for baseline factors) (Table 3, Figure 2). The effect size estimate was similar when baseline factors were not adjusted for (N=223; 148 events; P=0.003, per allele HR=1.44, 95% CI: 1.13–1.83) (Figure 1A).


IL8 polymorphisms and overall survival in pazopanib- or sunitinib-treated patients with renal cell carcinoma.

Xu CF, Johnson T, Garcia-Donas J, Choueiri TK, Sternberg CN, Davis ID, Bing N, Deen KC, Xue Z, McCann L, Esteban E, Whittaker JC, Spraggs CF, Rodríguez-Antona C, Pandite LN, Motzer RJ - Br. J. Cancer (2015)

Forest plot of meta-analysis association results between IL8 rs1126647 polymorphism and OS across three independent studies (with confirmation study 2 split into pazopanib- and sunitinib-treated subgroups). The HR was per variant T allele compared with reference A allele using an additive genetic model.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385958&req=5

fig2: Forest plot of meta-analysis association results between IL8 rs1126647 polymorphism and OS across three independent studies (with confirmation study 2 split into pazopanib- and sunitinib-treated subgroups). The HR was per variant T allele compared with reference A allele using an additive genetic model.
Mentions: In study 1 (pazopanib-treated, N=241), rs1126647 was significantly associated with OS (N=186; 125 events; P=0.007, per allele HR=1.45, 95% confidence interval (CI): 1.11–1.91; 18 patients had missing genotype data and 37 patients had missing data for baseline factors) (Table 3, Figure 2). The effect size estimate was similar when baseline factors were not adjusted for (N=223; 148 events; P=0.003, per allele HR=1.44, 95% CI: 1.13–1.83) (Figure 1A).

Bottom Line: In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8 × 10(-5); variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15-1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients.Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC.These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies.

View Article: PubMed Central - PubMed

Affiliation: GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.

ABSTRACT

Background: We evaluated germline single nucleotide polymorphisms (SNPs) for association with overall survival (OS) in pazopanib- or sunitinib-treated patients with advanced renal cell carcinoma (aRCC).

Methods: The discovery analysis tested 27 SNPs within 13 genes from a phase III pazopanib trial (N=241, study 1). Suggestive associations were then pursued in two independent datasets: a phase III trial (COMPARZ) comparing pazopanib vs sunitinib (N=729, study 2) and an observational study of sunitinib-treated patients (N=89, study 3).

Results: In study 1, four SNPs showed nominally significant association (P≤0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated (P≤0.05) with OS in study 2. Because rs1126647 and rs4073 were highly correlated, only rs1126647 was evaluated in study 3, which also showed association (P≤0.05). In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8 × 10(-5); variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15-1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients.

Conclusions: Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC. These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies.

Show MeSH
Related in: MedlinePlus