CTCs Plus Lactate Dehydrogenase Serve as Individual-Level Surrogate in Prostate Cancer

Circulating tumour cell counts together with lactate dehydrogenase levels may be used to assess treatment efficacy in men with metastatic prostate cancer

medwireNews: A biomarker panel comprising Circulating tumour cell (CTC) count and lactate dehydrogenase (LDH) level can function as a post-treatment surrogate for overall survival in patients with metastatic castration-resistant prostate cancer, research indicates.

These findings are based on the COU-AA-301 phase III trial that tested the efficacy of abiraterone acetate plus prednisone versus prednisone alone in this patient population.

“This trial is the first of a series of phase III studies designed to generate evidence to qualify a survival surrogate that can be used for regulatory submissions”, write Howard Scher, from Memorial Sloan Kettering Cancer Center in New York, USA, and colleagues in the Journal of Clinical Oncology. The combination of CTCs counts and LDH level, but neither one alone, reached “the rigorous criteria for surrogacy”, they say.

When the 711 men for whom biomarker data at week 12 were available were categorised into risk groups on the basis of this biomarker panel, the prednisone alone group had a significantly higher proportion of high-risk patients (CTCs ≥5 cells per 7.5 mL of blood and LDH >250 U/L) than the abiraterone acetate plus prednisone group, at 33% versus 15%. And a significantly lower proportion of low-risk patients (CTCs ≤4 per 7.5 mL of blood and any LDH level), at 48% versus 70%.

Median overall survival also varied significantly by risk group, at 8.71 months for high-risk, 12.02 months for intermediate-risk (CTCs ≥5 cells per 7.5 mL of blood and LDH ≤250 U/L) and 22.18 months for low-risk patients.

High-risk patients had an estimated 2-year survival rate of 2% – this compared with a survival rate of 10% in the intermediate-risk group and 46% in the low-risk group.

The weighted concordance index for the risk categories was 0.81, “a high value that provides strong evidence that the surrogate was able to discriminate survival time”, say the researchers.

"We await data from additional trials to test if the CTC plus LDH biomarker panel is valid for trial-level surrogacy and subsequent testing in prospective clinical trials”, they conclude.

Senior author Johann de Bono, from The Institute of Cancer Research in London, UK, said in a press release: “Our study showed that circulating tumour cells act as an early warning test for men who are not responding to treatment – potentially allowing doctors to switch patients early to alternative options. We hope our results will not only lead to better use of the current range of treatments, but also speed up the discovery of new drugs by providing an important new tool to the researchers trialling them.”

Reference

Scher HI, Heller G, Molina A, et al. Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. J Clin Oncol 2015; Advance online publication 23 March. doi:10.1200/JCO.2014.55.3487

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