This study examined whether or not a CTC change, PSA50, or the combination of the two variables could be used as a surrogate endpoint for overall survival in clinical trials. This study used the CellSearch® (Menarini) platform to count CTCs.
![UroToday_ASCOGU2019_Circulating Tumor Cell Number _1.png](/images/UroToday_ASCOGU2019_Circulating_Tumor_Cell_Number__1.png)
Data from 5 randomized mCRPC trials were included (shown above). PSA and CTC counts were collected at baseline and at 13 weeks, and overall survival was analyzed with respect to four variables: PSA50 (≥ 50% PSA decline from baseline), CTC0 (≥ 1 CTC/7.5 ml of blood at baseline and 0 CTCs at week 13), both PSA50 and CTC0, and either PSA50 or CTC0. A total of 6081 patients were analyzed from 5 clinical trials, of which 93% were alive at 13 weeks for measurement of CTCs and PSA. 3080 (54%) of patients had detectable CTCs at baseline.
![UroToday_ASCOGU2019_Circulating Tumor Cell Number _2.png](/images/UroToday_ASCOGU2019_Circulating_Tumor_Cell_Number__2.png)
In terms of overall survival analysis, change in CTCs from detectable to undetectable provided the greatest separation between responders and non-responders, more than PSA50 or the combination CTC change and PSA50.
![UroToday_ASCOGU2019_Circulating Tumor Cell Number _3.png](/images/UroToday_ASCOGU2019_Circulating_Tumor_Cell_Number__3.png)
CTC change from detectable to undetectable at week 13 may provide an early signal of benefit for patients with mCRPC and may actually provide a stronger measure of response compared with PSA50. However, there are significant limitations of this strategy. A significant number of patients do not have a detectable baseline CTC count and therefore may not be assessable using a CTC response measure. In the AFFIRM trial, 63% of patients did not have a baseline CTC. In this study, 46% of patients were not included due to CTC criteria.
![UroToday_ASCOGU2019_Circulating Tumor Cell Number _4.png](/images/UroToday_ASCOGU2019_Circulating_Tumor_Cell_Number__4.png)
Also, regardless of the biomarker, 14-18% of patients do not survive to 13 weeks, and this may bias any study that requires a week 13 biomarker. Additional prospective studies are necessary to see if CTC0 is predictive of overall survival in other disease states as well as with non-AR directed therapies.
Presented by: Howard I. Scher, MD, FASCO, Medical Oncologist, Co-Chair, Center for Mechanism Based Therapy; Head of the Biomarker Development Initiative; D. Wayne Calloway Chair in Urologic Oncology, Memorial Sloan Kettering Cancer Center
Discussant: William Kevin Kelly, DO
Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, Twitter: @TheRealJasonZhu at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA
References:
- Alix-Panabières C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer discovery 2016;6:479-91.
- 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. Journal of clinical oncology 2015;33:1348.
- Lorente D, Olmos D, Mateo J, et al. Circulating Tumor Cell Increase as a Biomarker of Disease Progression in Metastatic Castration-Resistant Prostate Cancer Patients with Low Baseline CTC Counts. Annals of Oncology 2018.
- 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. Journal of Clinical Oncology 2018;36:572.