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 Journal Article


Authors: Heller, G.; McCormack, R.; Kheoh, T.; Molina, A.; Smith, M. R.; Dreicer, R.; Saad, F.; de Wit, R.; Aftab, D. T.; Hirmand, M.; Limon, A.; Fizazi, K.; Fleisher, M.; de Bono, J. S.; Scher, H. I.
Article Title: 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
Abstract: Purpose Measures of response that are clinically meaningful and occur early are an unmet need in metastatic castration-resistant prostate cancer clinical research and practice. We explored, using individual patient data, week 13 circulating tumor cell (CTC) and prostate-specific antigen (PSA) response end points in five prospective randomized phase III trials that enrolled a total of 6,081 patients-COU-AA- 301, AFFIRM, ELM-PC-5, ELM-PC-4, and COMET-1-ClinicalTrials.Gov identifiers: NCT00638690, NCT00974311, NCT01193257, NCT01193244, and NCT01605227, respectively. Methods Eight response end points were explored. CTC nonzero at baseline and 0 at 13 weeks (CTC0); CTC conversion (5 CTCs at baseline, # 4 at 13 weeks-the US Food and Drug Administration cleared response measure); a 30%, 50%, and 70% decrease in CTC count; and a 30%, 50%, and 70% decrease in PSA level. Patients missing week-13 values were considered nonresponders. The discriminatory strength of each end point with respect to overall survival in each trial was assessed using the weighted c-index. Results Of the eight response end points, CTC0 and CTC conversion had the highest weighted c-indices, with smaller standard deviations. For CTC0, the mean (standard deviation) was 0.81 (0.04); for CTC conversion, 0.79 (0.03); for 30% decrease in CTC count, 0.72 (0.06); for 50% decrease in CTC count, 0.72 (0.06); for 70% decrease in CTC count, 0.73 (0.05); for 30% decrease in PSA level, 0.71 (0.03); for 50% decrease in PSA level, 0.72 (0.06); and for 70% decrease in PSA level, 0.74 (0.05). Seventyfive percent of eligible patients could be evaluated with the CTC0 end point, compared with 51% with the CTC conversion end point. Conclusion The CTC0 and CTC conversion end points had the highest discriminatory power for overall survival. Both are robust and meaningful response end points for early-phase metastatic castration-resistant prostate cancer clinical trials. CTC0 is applicable to a significantly higher percentage of patients than CTC conversion. © 2018 American Society of Clinical Oncology. All rights reserved.
Keywords: controlled study; survival rate; major clinical study; overall survival; united states; conference paper; comparative study; clinical practice; prostate specific antigen; randomized controlled trial; patient coding; clinical research; cell count; circulating tumor cell; castration resistant prostate cancer; human; male; priority journal
Journal Title: Journal of Clinical Oncology
Volume: 36
Issue: 6
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2018-02-20
Start Page: 572
End Page: 580
Language: English
DOI: 10.1200/jco.2017.75.2998
PROVIDER: scopus
PMCID: PMC5815402
PUBMED: 29272162
DOI/URL:
Notes: Conference Paper -- Export Date: 1 March 2018 -- Source: Scopus
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MSK Authors
  1. Glenn Heller
    298 Heller
  2. Martin Fleisher
    241 Fleisher
  3. Howard Scher
    832 Scher