Establishing a Short-term Response Endpoint for mCRPC Trials
After looking at 8 short-term endpoints based on PSA and CTCs, absence of tumor cells at week 13 was considered the best predictor of overall survival.
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After looking at 8 short-term endpoints based on prostate-specific antigen (PSA) and circulating tumor cells (CTCs), absence of tumor cells at week 13 (CTC0) was considered the best predictor of overall survival (OS), according to data presented at the 2007 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, Illinois.1
“With the many new treatments that are emerging in prostate cancer, we wanted to establish a short-term response endpoint that is reflective of survival in metastatic castration-resistant prostate cancer [mCRPC],” presenter Glenn Heller, MD, of the Memorial Sloan Kettering Cancer Center in New York, New York, said.
“It is important to develop an endpoint that is informative for survival and allows for completion of clinical trials in a short time,” he added.
Bone scans are hard to quantify and, currently, PSA is the most widely used endpoint, Dr Heller noted.
The investigators of the study evaluated several CTC parameters as potential endpoints across 5 large phase 3 studies. Four of the 5 have the androgen receptor as the target; 4 of the 5 had prednisone as an active control.
Each of the trials enrolled in excess of 1000 patients for a total of 5912 patients.
Eight potential short-term endpoints were analyzed based on PSA and CTC count. With respect to PSA, 30%, 50%, or 70% decrease in PSA at week 13 from baseline value (baseline PSA: at least 10) were considered. Similarly, for CTCs, 30%, 50%, or 70% decreases at week 13 from baseline values were considered (baseline CTC: at least 5).
Another CTC-related endpoint was CTC conversion from at least 5 at baseline to less than 5 at week 13, which has received US Food and Drug Administration (FDA) clearance as a diagnostic to monitor metastatic prostate cancer. The last CTC endpoint was CTC0 — for patients with CTC at least 1 at baseline and a CTC of 0 at week 13.
Patients with no 13-week data were considered non-responders. Across the studies in the analysis, 91% of patients had information for the PSA endpoints considered, 75% had CTC0 information, and 51% had the CTC30, CTC50, CTC70, and CTC conversion information.
For the CTC0 (mean weighted index: 0.81) and CTC conversion (mean weighted index 0.79) endpoints, survival information from each of the 5 studies tightly clustered together. For the other 6 putative endpoints, data from each of the 5 studies was “scattered,” with a mean weighted index between 0.71 and 0.74).
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“Responders have a better survival with CTC0,” Dr Heller said.
“Based on these data, CTC0 should be considered as a response endpoint for early phase clinical trials in metastatic prostate cancer,” Dr Heller concluded.
Read more of Cancer Therapy Advisor's coverage of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting by visiting the conference page.
- Heller G, Mccormack RT, Kheoh T, et al. Circulating tumor cell (CTC) number as a response endpoint in metastatic castration resistant (mCRPC) compared the PSA across fice randomized phase 3 trials. J Clin Oncol. 2017;35:(suppl: abstr 5007)