(ChemotherapyAdvisor) – Pretreatment serum lactate dehydrogenase (LDH) “is both a statistically significant prognostic factor in poor-risk patients with metastatic renal cell carcinoma (RCC) and also a predictive factor for the survival benefit conferred by the TORC1 inhibitor temsirolimus,” investigators reported in the Journal of Clinical Oncology online August 13.
Andrew J. Armstrong, MD, ScM, Duke Cancer Institute, Duke University Medical Center, Durham, NC, and colleagues retrospectively analyzed pretreatment and posttreatment serum LDH in 404 poor-risk patients with RCC who were randomized to temsirolimus or interferon alfa in a global phase 3 trial.
They found mean baseline serum normalized LDH to be 1.23 times the upper limit of normal (ULN). For patients with LDH more than 1 x ULN vs those with LDH ≤ 1 x ULN, multivariable hazard ratio for death was 2.81 (95% CI, 2.01–3.94; P<0.001).
“The LDH-treatment interaction term was statistically significant for OS [overall survival] (P=0.016),” they reported. “Among 140 patients with LDH above the ULN, OS was significantly improved with temsirolimus (6.9 vs 4.2 months; P<0.002). Among 264 patients with normal LDH, OS was not significantly improved with temsirolimus as compared with interferon therapy (11.7 vs 10.4 months; P=0.514).
Currently, no known predictive biomarkers for OS exist for clinical use in patients with RCC. “To the best of our knowledge, this analysis is the first to demonstrate that a baseline biomarker is predictive of OS in patients with genitourinary malignancies,” Dr. Armstrong noted.
They cautioned this analysis is limited to temsirolimus, with further study “needed to confirm and validate these findings prospectively in other RCC trials and other non-RCC tumor types. If validated, LDH as a predictive biomarker for this class of agents, and perhaps for agents that target the PI3K/Akt pathway, would be a substantial and clinically useful advance toward more personalized medicine without adding substantially to cost,” they concluded.