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TARGET: biomarkers predicted OS in RCC

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International Conference on Molecular Targets and Cancer Therapeutics

Several plasma biomarkers have been identified that may be predictive of OS in advanced renal cell carcinoma, according to the results of the TARGET study.

As an exploratory component of the TARGET study, researchers examined plasma biomarkers for possible prognostic value. The phase-3 TARGET trial found that sorafenib (Nexavar, Bayer), a multikinase inhibitor with activity against RAF kinase and a number of receptor tyrosine kinases, was safe and effective for patients with advanced renal cell carcinoma in whom one prior systemic treatment had failed.

In the study, 903 patients with advanced clear cell renal cell carcinoma were randomly assigned 1:1 to sorafenib or placebo. The results indicated that those patients assigned sorafenib had double the PFS as those assigned placebo.

Researchers then conducted a secondary analysis that measured plasma VEGF, soluble VEGFR-2, CAIX, TIMP-1 and p21 RAS by ELISA at baseline, three weeks and 12 weeks after treatment in order to determine if any of these biomarkers predicted outcome.

“The biomarker component of TARGET was intended to utilize this valuable study to search for biomarkers — in this case, proteins we can measure in plasma — that would help determine renal cell carcinoma prognosis, and predict patients who would benefit from treatment with sorafenib,” according to Coral Peña, PhD, associate director for Clinical Cancer Biomarkers at Bayer HealthCare Pharmaceuticals.

A previous report had shown that baseline VEGF was prognostic and possibly predictive of sorafenib benefit. However, results from this study indicate that there was no correlation between levels of plasma soluble VEGFR-2, CAIX, TIMP-1 or RAS and the efficacy of sorafenib.

In univariate analyses, patients with higher levels of CAIX (HR=2.26), TIMP-1 (HR=3.34) or RAS (HR=2.49) at the start of the trial had poorer OS when treated with placebo. An analysis of CAIX, TIMP-1, RAS and VEGF together with clinical variables in a group of 59 patients from the placebo group showed that TIMP-1 was independently prognostic for survival (P<.001).

In addition, the researchers found no correlation between the use of sorafenib and baseline levels of soluble VEGFR-2, CAIX, TIMP-1, or RAS. There was also no correlation found between outcome and change from baseline at three or 12 weeks for VEGF, soluble VEGFR-2, CAIX, TIMP-1 or RAS.

“For the moment, these findings are preliminary, but promising,” Pena said. “Although the analysis included a relatively small number of patients, the strength of TIMP-1 as a prognostic marker for renal cell carcinoma is remarkable. It would be interesting to see further studies of TIMP-1 in RCC to confirm this finding and evaluate its potential for clinical application.”

For more information:

• Pena C. #A36. Presented at: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; Nov. 15-19, 2009; Boston.