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Common enzyme predicted treatment progression of patients with kidney cancer
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The enzyme lactate dehydrogenase may predict how well patients with metastatic renal cell carcinoma will respond to a specific treatment, according to study results.
The findings could help personalize treatment to individual patients, sparing them from unnecessary drug regimens that offer no benefit while potentially causing adverse effects, the researchers wrote.
Elevated levels of serum lactate dehydrogenase (LDH) are associated with poor prognosis for patients with cancer, including renal cell carcinoma (RCC).
Researchers examined whether serum LDH was a prognostic tool and had a predictive value in patients with advanced kidney cancer who are treated with the mTOR inhibitor temsirolimus (Torisel, Wyeth Pharmaceuticals).
In a retrospective analysis of an international, phase 3, randomized trial, Andrew Armstrong, MD, MSc, associate professor of medicine and surgery at Duke University Medical Center, and colleagues evaluated pretreatment and treatment serum LDH in 404 poor-risk patients with RCC who were treated with the temsirolimus (n=203) or interferon-alpha (n=201).
“We found that pretreatment serum LDH is both a statistically significant prognostic factor in poor-risk patients with metastatic RCC and also a predictive factor for the survival benefit conferred by [temsirolimus],” Armstrong and colleagues wrote.
Patients treated with temsirolimus experienced significantly longer OS than patients treated with interferon-alpha (HR=0.76, 95% CI, 0.60-0.96; P=.02). Median OS was 10.6 months (95% CI, 8.5-12.1) for patients in the temsirolimus group vs. 7.1 months for patients assigned to interferon-alpha (95% CI, 5.9-8.8).
Among patients with high LDL levels at baseline, median OS was 6.9 months (95% CI, 5.1-10.7) for those treated with temsirolimus vs. 4.2 months for those treated with interferon-alpha (95% CI, 2.8-6.0).
The survival benefit among high-level LDL patients continued over time. At 6 months, 53.7% of high-level LDH patients assigned to temsirolimus were alive vs. 39.5% of those assigned to interferon-alpha. At 12 months, 34.3% of those assigned to temsirolimus were alive vs. 12.7% of those treated with interferon-alpha.
Researchers did not observe a similar survival benefit among patients with low LDH levels at baseline (HR=0.90; 95% CI, 0.67-1.22; P=.51). Among those patients, median survival was 11.7 months for those treated with temsirolimus vs. 10.4 months for those treated with interferon-alpha.
“This is an exciting finding,” Armstrong said in a press release. “In breast cancer, we can test for HER-2 expression and offer effective treatments based on that. Having a similar biomarker for kidney cancer that could direct patients to the best therapies for their cancer would be a major step forward.”
Additional trials are needed to validate the study findings and determine whether LDH may predict the success of other drugs that target cancers, Armstrong said.
Disclosure: The researchers report financial relationships with AVEO Pharmaceuticals, Bayer Pharmaceuticals, Genentech, GlaxoSmithKline, Novartis and Pfizer.
Perspective
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Brian I. Rini, MD
This is a biologically interesting study. In the big picture, we are certainly looking for biomarkers that can predict activity of a specific drug in kidney cancer. These data are interesting in that they may help us identify patients who are more sensitive to mTOR inhibition. This is retrospective and based on a certain subset of patients, so I think the data needs to be regarded as hypothesis-generating. Hopefully it will be validated in a prospective fashion. We are not really treating people with interferon anymore, so we would need to know if LDH predicts response to VEGF-targeted therapy, as well. A good biomarker allows you to pick one drug over another drug (eg, an mTOR inhibitor vs. a VEGF inhibitor). Prospective investigation is needed to determine whether this particular biomarker allows us to select patients for a specific treatment. Hopefully this analysis and future investigation can move the field forward in this regard.
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