Biomarker predicts temsirolimus benefit in renal cancer

By Andrew Czyzewski, medwireNews Reporter

In patients with metastatic renal cell carcinoma (RCC), the biomarker serum lactate dehydrogenase (LDH) is both prognostic for survival and predictive for the survival benefit conferred by the TORC1 inhibitor temsirolimus, research shows.

If validated, LDH "may help individually tailor therapy to those patients most likely to benefit, while reducing side effects by avoiding use of an agent in patients predicted to derive more limited or no benefit," the researchers note.

Andrew Armstrong (Duke University, Durham, North Carolina, USA) and colleagues initiated an international phase III randomized trial to evaluate pretreatment and post-treatment serum LDH in 404 RCC patients treated with the TORC1 inhibitor temsirolimus (n=201) or interferon alfa (IFN-α; n=203).

In all patients, baseline serum LDH was collected within 28 days prior to initiation and then post-hoc analyses were performed using the cutoff of normalized LDH above the upper limit of the normal range (ULN). Logistic regression was used to test for LDH-treatment interaction in predicting clinical benefit rate.

Armstrong and colleagues report that patients with the higher level of LDH had a significantly diminished survival rate compared with their peers with lower values (the multivariable hazard ratio for death was 2.81 for patients with LDH >ULN versus lower values).

In the 140 patients with LDH above the ULN, overall survival was significantly improved with temsirolimus relative to IFN-α (6.9 vs 4.2 months).

By contrast, among 264 subjects with normal LDH, overall survival was not significantly improved with temsirolimus compared with interferon therapy (11.7 vs 10.4 months).

Armstrong and colleagues say there are a number of possible mechanisms by which LDH could have a predictive effect.

Notably, elevated LDH may also reflect aberrant oncogene activity, as it is known that myc and PI3K/Akt/mTOR pathways regulate cellular LDH expression levels. Thus, TORC1 inhibitors may be selectively advantageous in tumor types with high LDH expression due to activation of these oncogenic pathways.

In any event the researchers conclude that "the advantage of LDH as a predictive and prognostic biomarker rests in its ease of collection, cost, and its routine assessment as part of routine medical care in patients with RCC."

The research is published in the Journal of Clinical Oncology.

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