Circulating tumor cell (CTC) rise and outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) with low baseline CTC counts.

David Lorente, David Olmos, Joaquin Mateo, Zafeiris Zafeiriou, Pasquale Rescigno, Diletta Bianchini, Niven Mehra, Arturo Molina, Thian Kheoh, Kurt Baeten, Robert Thomas Mccormack, Leon W.M.M. Terstappen, Howard I. Scher, Johann S. de Bono

Research output: Contribution to journalMeeting AbstractOther research output

Abstract

Background: CTCs are prognostic in CRPC. Baseline (BL) CTC < 5 CTCs/7.5mL are associated with improved prognosis. We have previously shown that a post-treatment 30% decline in CTC is associated with improved survival (OS) in patients with high (≥5) BL CTCs. We investigated the value of a rise in CTCs during the first 12-weeks (wks) of treatment in the COU-AA-301 (abiraterone) and IMMC-38 (chemotherapy) trial datasets in patients with low (<5) baseline CTC counts.

Methods: CTC of patients (pts) were determined using the CELLSEARCH (Janssen Diagnostics, LLC) platform. Pts with BL CTCs <5, and CTCs at 4, 8 or 12 weeks were evaluated. CTC progression (CTCrise) was defined as any increase in CTCs relative to BL at any of the 3 timepoints (4,8,12 wks). Landmark survival analyses at 12 wks were performed. Association of CTCrise with OS was evaluated with Cox regression in multivariable (MV) analysis (ECOG, LDH, ALP, Alb, Hb, BL CTC and PSA as covariates). Logistic regression was used to evaluate association with PSA response.

Results: 509 pts (419 in COU-301 and 90 in IMMC38) were identified as having a BL CTC<5; BL CTC was 0 in 257 pts (50.7%). Overall, median OS was 21.9m (95%CI:20.6-23.3). 212 pts (41.7%) experienced a CTCrise within 12-weeks of starting treatment; of these, 117 (55%) had a CTCrise as early as 4 weeks post-treatment. OS was significantly reduced (27.1 vs 15.2 months; HR: 3.5; 95%CI 2.6-4.7) in patients with a CTCrise in these first 12-weeks. Both BL CTC (log-transformed) and CTCrise were independently associated with OS in the MV survival model. Furthermore, a PSA rise of ≥25% from baseline at 12 wks was more frequent in pts with a CTC rise vs. no rise (46.9% vs 14%, p<0.001)

Conclusions: BL CTC and CTC rises are independently associated with OS in CRPC pts with low (<5) BLCTC treated with abiraterone and chemotherapy. These findings will require prospective validation

Original languageEnglish
Pages (from-to)5042-5042
JournalJournal of clinical oncology
Volume34
Issue number15
Publication statusPublished - 20 May 2016
Event52nd ASCO Annual Meeting 2016: Collective Wisdom: The Future of Patient-Centered Care and Research - McCormick Place, Chicago, United States
Duration: 3 Jun 20167 Jun 2016
Conference number: 52

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