Considerations in the development of circulating tumor cell technology for clinical use

Abstract

This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC) technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development-analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA) and the US National Cancer Institute (NCI).

Figure 1

Schema of Southwest Oncology Group (SWOG) Study S0500. This clinical study is evaluating the use of CTC levels in managing the treatment of metastatic breast cancer patients. Baseline CTC levels are determined using the CellSearch System™. Patients with CTC levels <5 CTCs/7.5 ml receive no further therapy, but are followed for progression-free survival (PFS) and overall survival (OS) (Arm A). For the remaining patients (≥ 5 CTCs/7.5 ml blood), CTCs are measured at specified time points during the course of chemotherapy. Patients with <5 CTCs/7.5 ml blood at 22 weeks continue with their current chemotherapy (Arm B). Patients with ≥5 CTCs/7.5 ml blood at this time point are randomized to current therapy (Arm C1) or a different therapy (Arm C2). Patients are followed for PFS and OS. (Reprinted by permission from the American Association for Cancer Research: Hayes DF, Smerage J: Is there a role for circulating tumor cells in the management of breast cancer? Clin Cancer Res 2008, 14 (12):3646–3650 DOI:http://dx.doi.org/10.1158/1078-0432.CCR-07-4481. See reference [64]).