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Plasma TIMP-1 predicts survival in advanced renal cell carcinoma

Megan Brooks

Last Updated: 2009-11-19 15:28:01 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Plasma levels of TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) are independently prognostic of overall survival in patients with advanced renal cell carcinoma (RCC), according to data presented yesterday at the 2009 Molecular Targets and Cancer Therapeutics International Conference in Boston.

The finding comes from an exploratory biomarker analysis of a subset of patients in the phase III TARGET study (Treatment Approach in Renal Cancer Global Evaluation Trial).

In this trial, compared to placebo, the multikinase inhibitor sorafenib doubled progression-free survival and significantly improved overall survival in patients with advanced RCC who had failed one previous treatment.

Before treatment with either sorafenib or placebo, and at 3 and 12 weeks of treatment, the researchers measured plasma biomarkers that could potentially predict clinical outcome, including VEGF, CAIX, TIMP-1 and p21 Ras.

The lead investigator, Dr. Carol Pena of Bayer Healthcare Pharmaceuticals in Montville, New Jersey, reported that in univariate analysis, "elevated levels of any of these biomarkers correlated with shorter survival in the absence of treatment."

Specifically, using the median baseline level of each biomarker to define high versus low levels, the hazard ratios for elevated VEGF, CAIX, TIMP-1 and p21 Ras were 1.65, 2.26, 3.34 and 2.49, respectively.

In a multivariate analysis of 59 patients, "only TIMP-1 retained independent prognostic value, at a very good p value of < 0.001," Dr. Pena reported.

She also noted that TIMP-1 levels decreased in sorafenib-treated patients and increased in placebo-treated patients during the course of treatment. "This could suggest that plasma TIMP-1 may be indicative of disease progression," Dr. Pena told the conference.

"This is the first demonstration that I could find in the literature of plasma TIMP-1 being a prognostic factor for RCC," she said, adding: "It has been shown that TIMP-1 correlates with survival and other outcome measures in other tumor types...but this is the first correlation of plasma TIMP-1 and survival in RCC."

TIMP-1, Dr. Pena said, "could facilitate a more personalized approach to RCC treatment."

The 2009 Molecular Targets and Cancer Therapeutics International Conference is jointly sponsored by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organization for Research and Treatment of Cancer (EORTC).

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