Circulating tumor cell (CTC) counts correspond with overall survival (OS) among patients with early-phase metastatic castration-resistant prostate cancer (mCRPC), according to a study published in the Journal of Clinical Oncology.1
Treatment modalities are changing rapidly for patients with mCRPC, creating a need for more robust and reliable endpoints to determine the benefit of clinical interventions. It is unclear, furthermore, whether prostate-specific antigen (PSA) testing is still the best surrogate marker for survival.
For this study, researchers assessed CTC and PSA response endpoints in 6081 patients enrolled in 1 of 5 prospective randomized phase 3 studies: COU-AA-301 (ClinicalTrials.gov Identifier: NCT00638690), AFFIRM (ClinicalTrials.gov Identifier: NCT00974311), ELM-PC5 (ClinicalTrials.gov Identifier: NCT01193257), ELM-PC4 (ClinicalTrials.gov Identifier: NCT01193244), and COMET-1(ClinicalTrials.gov Identifier: NCT01605227).
Eight CTC and PSA response measures were investigated: CTC0 (patients with a CTC count of 1 or higher at baseline and 0 at week 13), CTC conversion (CTCconv; patients with a CTC of count 5 or higher at baseline and 4 or fewer at week 13), and 3 measures of percent change for CTC (CTC counts of 5 or greater at baseline and a 30%, 50%, or 70% decline from baseline to week 13, respectively) and PSA (PSA level 5 ng/mL and greater at baseline and a 30%, 50%, or 70% decline from baseline to week 13, respectively).
CTC0 and CTCconv were the most useful markers for differentiating survival outcomes between responders and non-responders at week 13. The average weighted c-indices for CTC0 and CTCconv were 0.81 and 0.79, respectively. Weighted c-indices ranged from 0.5 to 1.0; a higher index indicated a greater probability of longer survival for patients who responded to treatment.
Having no detectable CTCs after treatment or converting from a higher level to fewer than 5 were better for discriminating patient survival compared with the percent change measures for CTC or PSA. Both measures allowed for broad eligibility, but more patients were evaluable with CTC0 (75%) vs CTCconv (51%).
The authors concluded that CTC0 provides “objective and reliable evidence that the therapy being administered has altered the patient’s prognosis in a favorable way. Taken together, the results of this study support the use of CTC0 as a response end point in early-phase clinical trials.”
- Heller G, McCormack R, Kheoh T, et al. Circulating tumor cell number as a response measure of prolonged survival for metastatic castration-resistant prostate cancer: a comparison with prostate-specific antigen across five randomized phase III clinical trials. J Clin Oncol. 2017 Dec 22. doi: 10.1200/JCO.2017.75.2998 [Epub ahead of print]