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Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis.

Publication ,  Conference
George, DJ; Martini, J-F; Staehler, MD; Chang, Y-H; Breza, J; Patard, J-J; Motzer, RJ; Magheli, A; Carteni, G; Donskov, F; Escudier, B; Li, S ...
Published in: Journal of Clinical Oncology
February 20, 2018

576 Background: In the phase III S-TRAC trial, adjuvant sunitinib (SU) prolonged disease-free survival (DFS) vs placebo (PBO) in patients with locoregional renal cell carcinoma at high risk of recurrence after nephrectomy (median 6.8 vs 5.6 y; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59–0.98; P= 0.03). An exploratory analysis evaluated associations between single nucleotide polymorphisms (SNPs) in angiogenesis-related genes and clinical outcomes in S-TRAC. Methods: Prospectively collected blood samples were genotyped for 10 SNPs and 1 insertion/deletion mutation with TaqMan assays. DFS was compared with a log-rank test for each SNP genotype in SU vs PBO arms and between SNP genotypes within each arm. P-values are unadjusted for multiplicity comparison. Results: Of 615 patients, 286 (142 SU; 144 PBO) were analyzed. There were generally no genotype frequency deviations from the Hardy-Weinberg equilibrium, but linkage disequilibrium was seen between VEGFA rs699947 and rs833061 on chromosome 6 (D′ = 1.000, r2 = 0.979). Longer DFS was observed with SU vs PBO for VEGFR1 rs9554320 C/C (median: not reached [NR] vs 5.56 y; HR 0.44, 95% CI 0.21–0.91; P= 0.023), VEGFR2 rs2071559 T/T (median: NR vs 4.47 y; HR 0.46, 95% CI 0.23–0.90; P= 0.020), and eNOS rs2070744 T/T (median: 7.07 vs 3.44 y; HR 0.53, 95% CI 0.30–0.94; P= 0.028), with a trend for VEGFR1 rs9582036 A/A (median: NR in both arms; P= 0.054) and SH3GL2 rs10963287 C/T (median: NR vs 5.35 y; P= 0.088). Shorter DFS was observed for VEGFR1 rs9582036 C/A vs C/C in the SU, PBO, and combined arms ( P< 0.05); for A/A vs common, the association was only seen in the SU arm ( P= 0.022). VEGFR1 rs9554320 A/C was associated with shorter DFS vs A/A in the PBO ( P= 0.038) and combined arm ( P= 0.006), with a trend in the SU arm ( P= 0.051). VEGFR2 rs1870377 T/T was associated with longer DFS vs A/A in the combined arms, but not in the PBO arm (n = 7 with A/A genotype in the SU arm precluded statistical tests). Conclusions: Correlations between common VEGFR1 and VEGFR2 SNPs and longer DFS with SU suggest germline SNPs are predictive of improved outcomes with adjuvant SU. Due to the exploratory nature of this analysis, prospective validation studies are needed to confirm these findings. Clinical trial information: NCT00375674.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2018

Volume

36

Issue

6_suppl

Start / End Page

576 / 576

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
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MLA
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George, D. J., Martini, J.-F., Staehler, M. D., Chang, Y.-H., Breza, J., Patard, J.-J., … Ravaud, A. (2018). Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis. In Journal of Clinical Oncology (Vol. 36, pp. 576–576). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2018.36.6_suppl.576
George, Daniel J., Jean-Francois Martini, Michael D. Staehler, Yen-Hwa Chang, Jan Breza, Jean-Jacques Patard, Robert J. Motzer, et al. “Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis.” In Journal of Clinical Oncology, 36:576–576. American Society of Clinical Oncology (ASCO), 2018. https://doi.org/10.1200/jco.2018.36.6_suppl.576.
George DJ, Martini J-F, Staehler MD, Chang Y-H, Breza J, Patard J-J, et al. Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2018. p. 576–576.
George, Daniel J., et al. “Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis.Journal of Clinical Oncology, vol. 36, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. 576–576. Crossref, doi:10.1200/jco.2018.36.6_suppl.576.
George DJ, Martini J-F, Staehler MD, Chang Y-H, Breza J, Patard J-J, Motzer RJ, Magheli A, Carteni G, Donskov F, Escudier B, Li S, Casey M, Valota O, Laguerre B, Pantuck AJ, Pandha HS, Patel A, Lechuga M, Ravaud A. Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2018. p. 576–576.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2018

Volume

36

Issue

6_suppl

Start / End Page

576 / 576

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences