Post Hoc Analysis of COU-AA-301: CTC as Response Criterion

Chicago—Use of RECIST (Response Evaluation Criteria in Solid Tumors) to assess radiographic response in the majority of patients with metastatic castration-resistant prostate cancer (mCRPC) is limited by the lack of measurable disease. Changes in circulating tumor cell (CTC) counts enumerated by Veridex CellSearch from “unfavorable” at baseline (≥5 cells/7.5 mL) to “favorable” (≤4 cells/7.5 mL) are prognostic for survival.

The US  FDA has cleared the test as an aid in managing and monitoring mCRPC. However, according to Howard I. Scher, MD, and colleagues, many patients are excluded from response assessment by the CTC cutpoint of ≥5 cells/7.5 mL. A secondary end point of COU-AA-301, a phase 3 trial of abiraterone acetate plus prednisone versus prednisone alone in patients with mCRPC, was the examination of CTCs alone and in combination with other biomarkers as a potential surrogate for clinical benefit.

Dr. Scher et al. reported results of a post hoc analysis of data from COU-AA-301 during a poster session and discussion at the 2017 ASCO Annual Meeting. The poster was titled Clinical Outcomes of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients with a Post-Treatment Circulating Tumor Cell of 0 vs CTC >0: Post Hoc Analysis of COU-AA-301.

In the current analysis, patients from both treatment groups with baseline CTC >0 were combined to assess CTC=0 as a criterion for response. The analysis was designed to assess the association between CTC response, defined as baseline CTC >0 and post-baseline CTC=0, as well as other clinical outcomes. CTCs were determined at baseline and weeks 4, 8, and 12. Nonresponders were defined as patients with baseline CTC >0 and those missing post-treatment CTCs.

Radiographic response was initially measured at week 12. The Kaplan-Meier Method was used to estimate overall survival.

Of 739 patients with baseline CTC >0, 141 had measurable disease. At week 12, 141 of 739 (19%) were CTC responders and 598 of 739 (81%) were nonresponders. Of those considered responders, 104 of 141 (74%) had stable disease or better by RECIST; 37 of the 141 (26%) were either not evaluable or had disease progression by RECIST. Median overall survival was 23.8 months for responders (n=141) and 10.0 months for nonresponders (n=598).

Of patients with liver and/or lung metastases, 24 of 28 (86%) CTC responders at week 12 had stable disease or better by RECIST; 4 of the 28 (14%) had disease progression by RECIST. Median overall survival was 19.9 months for responders (n=28) and 7.1 months for nonresponders (n=127). In week 8 CTC responders, similar results were observed.

In conclusion, the researchers said, “For mCRPC patients with baseline CTC >0, CTC response on treatment (CTC=0) is associated with longer survival and could be considered a response criterion. Additional analysis is required to fully characterize the relationship between CTC=0 and objective response by RECIST in patients with measurable disease.”

Source: Scher HI, Heller G, Yu MK, et al. Clinical outcome of metastatic castration