TY - JOUR
T1 - Circulating tumor cells in advanced cervical cancer
T2 - NRG oncology—gynecologic oncology group study 240 (NCT 00803062)
AU - Tewari, Krishnansu S.
AU - Sill, Michael W.
AU - Monk, Bradley J.
AU - Penson, Richard T.
AU - Moore, David H.
AU - Lankes, Heather A.
AU - Ramondetta, Lois M.
AU - Landrum, Lisa M.
AU - Randall, Leslie M.
AU - Oaknin, Ana
AU - Leitao, Mario M.
AU - Eisenhauer, Eric L.
AU - DiSilvestro, Paul
AU - van Le, Linda
AU - Pearl, Michael L.
AU - Burke, James J.
AU - Salani, Ritu
AU - Richardson, Debra L.
AU - Michael, Helen E.
AU - Kindelberger, David W.
AU - Birrer, Michael J.
N1 - Funding Information:
This study was supported by NCI grants to the GOG Tissue Bank (U10 CA27469 and U24 CA114793), NRG Oncology (1U10 CA180822), and NRG Operations (U10CA180868).
Funding Information:
K.S. Tewari reports grants from University of California, Irvine during the conduct of the study; personal fees from Roche/Genentech (advisory board, consultant) outside the submitted work. B.J. Monk reports personal fees from Abbvie (honorarium/consultant), Advaxis (honorarium/consultant), Agenus (honorarium/consultant), Amgen (honorarium/consultant), Akeso Bio (honorarium/consultant), Aravive (honorarium/consultant), AstraZeneca (honorarium/consultant/speaker), Asymmetric Therapeutics (honorarium/ consultant), Boston Biomedical (honorarium/consultant), ChemoCare (honorarium/ consultant), ChemoID (honorarium/consultant), Circulogene (honorarium/consultant), Clovis (honorarium/consultant/speaker), Conjupro (honorarium/consultant), Dice-pheria (honorarium/consultant), Easai (honorarium/consultant), Geistlich (honorarium/consultant), Genmab/Seatlle Genetics (honorarium/consultant), GOG Foundation (honorarium/consultant), ImmunoGen (honorarium/consultant), Immunomedics (honorarium/consultant), Incyte (honorarium/consultant), Iovance (honorarium/consultant), Janssen/Johnson & Johnson (honorarium/consultant/speaker), Laekna Health Care (honorarium/consultant), Mateon (formally Oxigene) (honorarium/consultant), Merck (honorarium/consultant/speaker), Mersana (honorarium/consultant), Myriad (honorarium/consultant), Nucana (honorarium/consultant), Oncomed (honorarium/consultant), Oncoquest (honorarium/consultant), Oncosec (honorarium/consultant), Perthera (honorarium/consultant), Pfizer (honorarium/consultant), Precision Oncology (honorarium/ consultant), Puma (honorarium/consultant), Regeneron (honorarium/consultant), Roche/Genentech (honorarium/consultant/Sseaker), Samumed (honorarium/consultant), Takeda (honorarium/consultant), Tarveda (honorarium/consultant), TESARO/ GSK (honorarium/consultant/speaker), Vavotar Life Sciences (honorarium/consultant), VBL (honorarium/consultant), and Vigeo (honorarium/consultant) outside the submitted work. R.T. Penson reports grants and personal fees from Genentech Roche during the conduct of the study; personal fees and other from AbbVie (DSMC); grants and personal fees from AstraZeneca, Clovis Oncology, Eisai Inc, Merck & Co, NewLink Genetics, Tesaro Inc, and Vascular Biogenics Ltd; nonfinancial support from Care4ward; personal fees from Curio Science, Janssen Oncology, Mersana Therapeutics, Nexus Global Group, Pieris Pharma Inc, and Sutro Biopharma; grants from Syndax Pharmaceuticals, outside the submitted work. L.M. Randall reports grants from University of California Irvine during the conduct of the study; grants and personal fees from GSK/Tesaro and Merck; grants from Pfizer, OnTarget Laboratories, Aivita Biopharma; personal fees from Clovis Oncology, Myriad, AstraZeneca, outside the submitted work. A. Oaknin reports personal fees from Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, Inmunogen, and Genmab outside the submitted work. M.M. Leitao reports personal fees from Intuitive Surgical (ad hoc speaker) outside the submitted work. M.L. Pearl reports grants from GOG/NRG Oncology (NCI) during the conduct of the study; other from Vita-Tex, Inc (royalties via Stony Brook Foundation) outside the submitted work; and conducted NIH-funded research on circulating tumor cells in patients with ovarian cancer with researchers from Vita-Tex, a start-up company owned by my research collaborator. During that time, I received royalties ($500/year) from the Stony Brook Foundation. Vita-Tex was purchased last year and my collaboration is currently on hold. R. Salani reports other from Clovis (advisory board) and other from GlaxoSmithKline (advisory board) outside the submitted work. D.L. Richardson reports personal fees from AstraZeneca, Foundation Medicine, GSK/Tesaro, Mersana, Deciphera, Bayer, and Genentech outside the submitted work. No potential conflicts of interests were disclosed by the other authors.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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-cytokeratinþ/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.
AB - 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-cytokeratinþ/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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85100509042&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-20-0276
DO - 10.1158/1535-7163.MCT-20-0276
M3 - Article
C2 - 32847980
AN - SCOPUS:85100509042
SN - 1535-7163
VL - 19
SP - 2363
EP - 2370
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
IS - 11
ER -