Abstract 1727: Circulating Tumor Cells (CTCs) in patients with extensive stage small cell lung cancer and their association with clinical outcome
Authors: Chun Zhang, Ryon Graf, Adam Jendrisak, Amanda K. Anderson, Priscilla Ontiveros, Sarah Orr, Anne Chiang, David Spigel, Charles Rudin, Eric Holmgren, Jakob Dupont, Gretchen Argast, Leonardo Faoro, Lei Zhou, John Lewicki, Ann M. Kapoun
Journal: Cancer Research (2017)

Abstract Background: The NOTCH pathway has been identified as a key therapeutic pathway in SCLC. Tarextumab (TRXT, anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. PINNACLE is a Phase 1b/2 trial of TRXT in combination with etoposide and platinum therapy (EP) in patients with untreated extensive stage small cell lung cancer (ES-SCLC). Baseline CTCs and post treatment changes in CTCs have previously been shown to predict the response to chemotherapy in SCLC. CTCs may also serve as pharmacodynamic biomarkers. Here we describe a study of baseline and longitudinal CTCs in ES-SCLC patients from the PINNACLE phase 1b trial (clinicaltrials.gov:NCT01859741). Materials and methods: CTCs, CTC clusters, apoptotic CTCs and N-Cadherin+ CTCs were identified and enumerated from patient blood samples using Epic Sciences CTC technology. Baseline CTCs from 26 patients were correlated with clinical outcome: progression-free survival (PFS), overall survival (OS) and best overall response, as well as metastatic status. A mixed effects model was used to investigate the post treatment changes in CTCs among the dose groups. Association of CTCs with PFS/OS and best overall response, including CTCs at each time point, as well as temporal changes of CTC status, were studied. Multivariate analysis was performed to identify CTC numbers in a subset of time points to correlate with response to treatment. Results: CTCs were present in 81% of the patients (21/26). CTC clusters and apoptotic CTCs were detected in 38% and 77% of the patients, respectively. At baseline, CTC counts ≥ 5/mL were significantly associated with poor OS (p=0.04). There was a trend that the presence of CTC clusters was associated with worse OS. With a cut-off of 3.4/mL, apoptotic CTCs showed a trend in association with overall survival. CTC numbers in patients with liver metastasis were significantly higher than in patients without liver metastasis. CTCs were also found to be correlated significantly with the number of metastatic sites. When measuring at Day 7 post dosing, CTC numbers were significantly decreased. Conclusions: Our findings suggest that CTCs are frequently detectable in patients and are a prognostic factor in ES-SCLC. CTCs decrease with TRXT and platinum-based chemotherapy. Updated results will be presented. CTCs will be further evaluated in the phase 2 portion of the PINNACLE trial. Citation Format: Chun Zhang, Ryon Graf, Adam Jendrisak, Amanda K. Anderson, Priscilla Ontiveros, Sarah Orr, Anne Chiang, David Spigel, Charles Rudin, Eric Holmgren, Jakob Dupont, Gretchen Argast, Leonardo Faoro, Lei Zhou, John Lewicki, Ann M. Kapoun. Circulating Tumor Cells (CTCs) in patients with extensive stage small cell lung cancer and their association with clinical outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1727. doi:10.1158/1538-7445.AM2017-1727