7103 ORAL Association of Single Nucleotide Polymorphisms (SNPs) in VEGF Pathway Genes With Progression-free Survival (PFS) and Blood Pressure (BP) in Metastatic Renal Cell Carcinoma (mRCC) in the Phase 3 Trial of Axitinib Versus Sorafenib (AXIS Trial)

Abstract In patients with follicular lymphoma treated with single-agent rituximab, single nucleotide polymorphisms in the FCGR3A gene are known to influence response and progression-free survival. The prognostic role of FCGR3A and FCGR2A polymorphisms in patients with follicular lymphoma treated with rituximab and chemotherapy combination remains controversial and has not been evaluated in the context of rituximab maintenance. FCGR3A and FCGR2A single nucleotide polymorphisms were evaluated in, respectively, 460 and 455 patients treated in the PRIMA study to investigate whether these were associated with response rate and patient outcome after rituximab chemotherapy induction and 2-year rituximab maintenance. In this representative patient cohort, complete and unconfirmed complete responses after rituximab chemotherapy were observed in 65%, 67%, 66% (P = .86) and 60%, 72%, 66% (P = .21) of FCGR3A VV, VF, FF and FCGR2A HH, HR, RR carriers, respectively. After 2 years of rituximab maintenance (or observation), response rates did not differ among the different genotypes. Progression-free survival measured from either treatment initiation or randomization to observation or maintenance was not influenced by these polymorphisms. These data indicate that FCGR3A and FCGR2A polymorphisms do not influence response rate and outcome when rituximab is combined with chemotherapy or used as maintenance treatment. The PRIMA study is registered at www.clinicaltrials.gov as NCT00140582.

Download Full-text

Use of CA9 gene single nucleotide polymorphisms to predict prognosis and treatment response of metastatic renal cell carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5003 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5003-5003

Author(s):

M. de Martino ◽

T. Klatte ◽

D. B. Seligson ◽

J. LaRochelle ◽

B. Shuch ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Prognostic Factors ◽

Single Nucleotide Polymorphisms ◽

Protein Expression ◽

Renal Cell ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Allele Variant ◽

Caix Expression

5003 Background: Carbonic anhydrase 9 gene (CA9) is located in a prognostically relevant chromosomal area on chromosome 9p and is encoding for one of the most significant protein markers in metastatic renal cell carcinoma (MRCC), CAIX. In contrast to CAIX protein, however, no efforts have been made to date to study CA9 gene in metastatic RCC. Here, we test the hypotheses that single nucleotide polymorphisms (SNPs) and mutations of the CA9 gene are associated with CAIX expression, response to immunotherapy and survival. Methods: Genomic DNA was extracted from frozen tumor samples of 54 patients with clear cell MRCC. All exons of the CA9 gene were PCR-amplified and sequenced. The antibody M75 was used to evaluate CAIX protein expression immunohistochemically. Statistical associations of CA9 gene status and CAIX protein expression with response to IL-2 based immunotherapy and overall survival were assessed with chi-square tests, t-tests, Kaplan-Meier survival estimates and Cox proportional hazards regression models. Results: CA9 reference SNP (rs) 2071676 was found in 59%, rs12553173 in 15%, rs3829078 in 11% and rs1048638 in 33% of the patients. The deletion c.376del393 was observed in two patients. CAIX expression was high (>85%) in 65% of the patients. None of the SNPs was significantly associated with CAIX expression. Patients with the C allele variant of rs12553173 had improved median survival (27.3 vs. 13.6 months, p = 0.0431) and a greater likelihood of response to IL-2 (57% vs. 22%, p = 0.081) Likewise, high CAIX expression was associated with longer median survival (25.5 vs. 8.5 months, p < 0.0001) and a greater IL-2 response rate (37% vs. 8%, p = 0.070). In a multivariate Cox model, both C allele variant of CA9 SNP rs12553173 and CAIX expression were retained as independent prognostic factors. Conclusions: CA9 SNPs are frequently found in patients with MRCC. The C allele variant of rs12553173 is associated with improved overall survival and a greater likelihood of response to IL-2. CA9 rs12553173 and CAIX are both independent prognostic factors of overall survival and complementary in predicting prognosis of MRCC. No significant financial relationships to disclose.

Download Full-text