Circulating Tumor Cells In Advanced Cervical Cancer: NRG Oncology-Gynecologic Oncology Group Study 240 (NCT 00803062).

Abstract

To isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the antiangiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratin+/anti-CD45- cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semiautomated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0-18) and, at 36 days posttreatment, was 4 (range, 0-17). The greater the declination in CTCs between time points studied, the lower the risk of death [HR, 0.87; 95% confidence interval (CI), 0.79-0.95)]. Among patients with high (≥ median) pretreatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR, 0.57; 95% CI, 0.32-1.03) and PFS (HR, 0.59; 95% CI, 0.36-0.96). This effect was not observed with low (< median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pretreatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker.

• Authors: Krishnansu S Tewari, Michael W Sill, Bradley J Monk, Richard T Penson, David H Moore, Heather A Lankes, Lois M Ramondetta, Lisa M Landrum, Leslie M Randall, Ana Oaknin, Mario M Leitao, Eric L Eisenhauer, Paul DiSilvestro, Linda Van Le, Michael L Pearl, James J Burke, Ritu Salani, Debra L Richardson, Helen E Michael, David W Kindelberger, Michael J Birrer
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 19 Issue 11 Pg. 2363-2370 (11 2020) ISSN: 1538-8514 [Electronic] United States
• PMID: 32847980 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Biomarkers, Tumor
• Disease Management
• Female
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Molecular Targeted Therapy
• Neoplastic Cells, Circulating (pathology)
• Prognosis
• Treatment Outcome
• Uterine Cervical Neoplasms (diagnosis, etiology, mortality, therapy)