Can CTC counts be used as surrogate endpoints in clinical trials?

Intermediate or surrogate endpoints for survival can shorten timelines for drug approval. A paper just published on line in Lancet Oncology aimed to assess the value of circulating tumor cell (CTC) counts as a prognostic factor for survival.

Scher et al. identified patients with progressive, metastatic, castration-resistant prostate cancer starting first-line chemotherapy in a fully enrolled but still ongoing clinical trial.

CTCs were isolated from blood samples at baseline and after treatment. Baseline variables, including CTC count, PSA level, concentration of lactate dehydrogenase (LDH), and post-treatment variables (change in CTCs and PSA) were tested for association with survival.

The authors reported the following findings:

  • The variables associated with high risk of death were high LDH concentration (hazard ratio 6.44), high CTC count (hazard ratio 1.58), high PSA level (hazard ratio 1.26), low albumin (hazard ratio 0.10), and low haemoglobin (hazard ratio 0.72) at baseline.
  • At 4, 8, and 12 weeks after treatment, changes in CTC counts were strongly associated with risk, whereas changes in PSA level were weakly or not associated (p > 0.04).
  • The most predictive factors for survival were LDH concentration and CTC counts (concordance probability estimate 0.72—0.75).

The authors interpret these data to mean that the CTC count, analyzed as a continuous variable, can be used to monitor disease status and might be useful as an intermediate endpoint of survival in clinical trials. However, they clearly state that, “Prospective recording of CTC number as an intermediate endpoint of survival in randomized clinical trials is warranted.”

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