Declines in Top1-positive Circulating Tumor Cells Associated With Prolonged Survival After Etirinotecan Pegol

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Declines in topoisomerase-I (Top1)-positive circulating tumor cells might be a biomarker of prolonged survival in advanced breast cancer.
Declines in topoisomerase-I (Top1)-positive circulating tumor cells might be a biomarker of prolonged survival in advanced breast cancer.

SAN ANTONIO—Declines in topoisomerase-I (Top1)-positive circulating tumor cells (CTCs) might be a biomarker of prolonged survival among patients with advanced breast cancer following treatment with the Top1 inhibitor etirinotecan pegol (EP), according to an analysis presented the 2015 San Antonio Breast Cancer Symposium.1

“Consistent with the mechanism of action of EP as a Top1 inhibitor, improved overall survival (OS) was observed in patients receiving EP whose CTCs converted from high to low percept Top1 by the end of Cycle 1,” reported lead study author Hope S. Rugo, MD, of Baylor Sammons Cancer Center in Dallas, TX. “This change was not observed in patients on the control arm receiving treatment of physician's choice (TPC).”

EP provides prolonged exposure to SN38, the active metabolite, noted Dr Rugo. “The phase 3 BEACON trial compared EP to TPC in patients with advanced breast cancer, demonstrating a statistically insignificant 2.1 month difference in survival [numerically] favoring EP in the intent-to-treat population [P = .083, not significant].”

However, the BEACON trial also “explored the utility of CTC biomarkers” as predictors of treatment efficacy, Dr Rugo reported. For the CTC substudy, serial 7.5 mL whole blood samples were drawn at baseline, during the study, and at end-of-treatment, and shipped to ApoCell in Houston, TX, for processing, Dr Rugo reported. CTCs were collected and stained for analysis “for pharmacodynamic markers and antibodies CD45 and DAPI for phenotypic identification of CTCs.”

Biomarkers were quantified by iCys® laser scanning cytometer equipped with image analysis software, she added. Biomarker data associations with overall survival were then analyzed using multivariate and Kaplan-Meier statistical analyses.

The CTC substudy yielded 629 baseline, 534 C2D1, and 272 C4D1 samples, Dr Rugo reported.

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The researchers identified an association between post-treatment number of Top1-positive CTCs and overall survival (OS) among patients receiving EP. To further assess the impact of Top1-positive CTCs, patients were classified as Top1-High or Top1-Low (≤ median) based on the percent of Top1-positive CTCs at baseline.

Among the Top1-High [> median number of Top1-positive CTCs] patients at baseline, significantly improved OS (14.7 months vs 10.5 months; hazard ratio [HR] 0.57; P = .01) was observed for those who converted to Top1-Low [(≤ median] after their first treatment with EP—but not TPC (HR 1.10; P = .68).


  1. Rugo HS, Cortes J, Awada A, et al. Early change in topoisomerase 1 (Top1) positive circulating tumor cells (CTCs) is associated with overall survival (OS) in patients with advanced breast cancer after treatment with etirinotecan pegol. Oral presentation at: San Antonio Breast Cancer Symposium 2015; December 9, 2015; San Antonio, TX.

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