Early reduction in CTCs leads to survival benefit in prostate cancer

CHICAGO —A 30% decline in circulating tumor cells after 4 weeks of treatment yielded a survival benefit in patients with castration-resistant prostate cancer, according to findings presented at the ASCO Annual Meeting.

Perspective from Sumanta Pal, MD

Prior researchers has demonstrated circulating tumor cell (CTC) counts greater than 5/7.5mL are prognostic for worse survival, according to study background.

David Lorente, MD, of The Institute of Cancer Research and The Royal Marsden National Health Service Foundation Trust in Sutton, U.K., and colleagues investigated whether a 30% or greater decline in CTCs from baseline levels — which indicated a CTC response — after 4 and 12 weeks of treatment demonstrates an association with improved OS.

Researchers analyzed findings from the phase 3 COU-AA-301 study (n = 326) — in which patients received abiraterone (Zytiga, Janssen) — and the phase 3 IMMC-38 trial (n = 113), in which patients received chemotherapy.

Eligible participants had baseline CTC counts of 5 or greater and valid CTC count data after weeks 4 and 12 of treatment.

Patients in the COU-AA-301 study had a median baseline CTC count of 18.5 and patients in the IMMC-38 study had a median baseline CTC count of 23.

The median OS for all patients evaluated from COU-AA-301 was 11.6 months (95% CI, 10.3-13). Sixty-four percent of patients in that study reached the 30% CTC decline benchmark by week 4. Median OS among patients who demonstrated CTC response was 14.4 months (95% CI, 13.2-15.5), compared with 7.9 months (95% CI, 6.8-9) among those who failed to reach the 30% decline (HR = 0.4; 95% CI, 0.3-0.6).

In the IMMC-38 study, median OS was 11.2 months (95% CI, 9.7-12.6). A 30% decline in CTCs occurred in 66% of those patients by week 4. Patients who demonstrated CTC response achieved significantly longer median OS compared with patients who did not (12.3 months vs. 6.8 months;

HR = 0.5; 95% CI, 0.3-0.8).

The c-index — which indicated the value of the multivariate model’s ability to demonstrate an association with OS — improved from 0.677 to 0.712 in COU-AA-301 and from 0.747 to 0.800 in IMMC-38 after including CTC response.

The association between improved OS and CTC response persisted when researchers evaluated data after 12 weeks of treatment.

“We think that the clinical utility of this finding will be that we can identify patients for intervention with different treatments,” Lorente told HemOnc Today in an interview. — by Rob Volansky

Reference:

Lorente D, et al. Abstract 5014. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

For more information:

David Lorente, MD, can be reached at The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP.

Disclosure: Lorente reports no relevant financial disclosures. Please see the abstract for a complete list of the researchers’ relevant financial disclosures.

Perspective

Sumanta Pal, MD

At this point in time we use circulating tumor cells (CTCs) to identify prognosis in patients with advanced prostate cancer. We know that the number of CTCs found in the blood can actually be quite prognostic in this setting and can dictate whether a patient will have a good survival or poor survival outcome. The work done by Lorente and colleagues identifies something that goes beyond that, a potential predictive marker. In the context of abiraterone (Zytiga, Janssen) therapy, based on the rise or fall of tumor cells, we can now predict who will or will not respond. I think this is a key issue for us as we face an enlarging armamentarium of drugs for prostate cancer.

Sumanta Pal, MD

HemOnc Today Editorial Board member

City of Hope

Disclosures: Pal reports no relevant financial disclosures.