Christophe Massard1, Isabelle Borget2, Françoise Farace3, Sandrine Aspeslagh4, Marie-Cécile Le Deley2, Christophe Le Tourneau5, François-Clement Bidard6, Jean-Yves Pierga7, Veronique Dieras8, Paul Hofman9, Jean-Philippe Spano10, Charles Ferte4, Ludovic Lacroix11, Jean-Charles Soria12. 1. Drug Development Department (DITEP), Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France. Electronic address: christophe.massard@gustaveroussy.fr. 2. Faculty of Pharmacy, University Paris-Sud, Châtenay-Malabry, France; Department of Health Economics, Gustave Roussy Institute, Villejuif, France. 3. Platform of Rare Circulating Cells, AMMICA CNRS UMS3655 INSERM US23, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France; INSERM Unit U981, F-94805, Villejuif, France; Université Paris-Saclay, F-94270, Le Kremlin-Bicêtre, France. 4. Drug Development Department (DITEP), Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France. 5. Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud, France; INSERM U900 Research unit, Saint-Cloud, France. 6. Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud, France; Institut Curie, PSL Research University, SiRIC, Laboratory of Circulating Tumor Biomarkers, 75005, Paris, France. 7. Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud, France; Institut Curie, PSL Research University, SiRIC, Laboratory of Circulating Tumor Biomarkers, 75005, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France. 8. Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud, France. 9. Université Nice Côte d'Azur (UCA), Laboratory of Clinical and Experimental Pathology, FHU OncoAge, Pasteur Hospital and Hospital-related Biobank (BB-0033-00025), 06001, Nice, Cedex, France. 10. University Hospital Pitié Salpêtrière, Department of Medical Oncology, University Pierre and Marie Curie, INSERM_UMRS1136, Paris, France. 11. Gustave Roussy Cancer Campus, Department of Medical Biology and Pathology, Translational Research Laboratory and Biobank (UMS3655 CNRS /US23 INSERM), INSERM Unit U981, Villejuif, France. 12. Drug Development Department (DITEP), Gustave Roussy, 94805, Villejuif, France; Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Orsay, 91405, France.
Abstract
BACKGROUND: Circulating tumour cell (CTC) counting could be a new biomarker for better evaluation of tumour response to molecules tested in phase I trials. PATIENTS AND METHODS: Consenting patients with advanced metastatic cancer referred to various phase I units were enrolled prospectively in this study. CTCs from 7.5 ml of whole blood drawn at baseline and after starting experimental therapy were counted using the CellSearch system, and tumour response was assessed using RECIST 1.1 criteria at baseline and 2 months after treatment initiation. RESULTS: Between March 2010 and May 2013, a total of 326 patients were enrolled, among whom 214 were evaluable (49% male, median age = 56; main cancer types: lung [28], colon [53], ovarian [18], breast [28]). At baseline, we detected ≥1 CTC/7.5 ml in 113/214 patients (53%), and at day 30, we observed ≥1 CTC/7.5 ml in 103/214 patients (48%). Two months after treatment initiation, 11 (5%) of the 214 patients were classified as having a partial response, with no CTCs in 9 of them or a decrease in the CTC count after therapy. In contrast, among the 104 patients (49%) classified as having progressive disease, 38 patients had a higher CTC count. The remaining 99 patients (49%), 33 of whom (33%) had a lower CTC count, were classified as having stable disease. The sensitivity and specificity of CTC variation for predicting progressive disease were 41% (32-51%) and 80% (73-88%) respectively. CONCLUSION: An early CTC change following therapy does not correlate with RECIST response in patients with advanced cancer enrolled in phase I trials.
BACKGROUND: Circulating tumour cell (CTC) counting could be a new biomarker for better evaluation of tumour response to molecules tested in phase I trials. PATIENTS AND METHODS: Consenting patients with advanced metastatic cancer referred to various phase I units were enrolled prospectively in this study. CTCs from 7.5 ml of whole blood drawn at baseline and after starting experimental therapy were counted using the CellSearch system, and tumour response was assessed using RECIST 1.1 criteria at baseline and 2 months after treatment initiation. RESULTS: Between March 2010 and May 2013, a total of 326 patients were enrolled, among whom 214 were evaluable (49% male, median age = 56; main cancer types: lung [28], colon [53], ovarian [18], breast [28]). At baseline, we detected ≥1 CTC/7.5 ml in 113/214 patients (53%), and at day 30, we observed ≥1 CTC/7.5 ml in 103/214 patients (48%). Two months after treatment initiation, 11 (5%) of the 214 patients were classified as having a partial response, with no CTCs in 9 of them or a decrease in the CTC count after therapy. In contrast, among the 104 patients (49%) classified as having progressive disease, 38 patients had a higher CTC count. The remaining 99 patients (49%), 33 of whom (33%) had a lower CTC count, were classified as having stable disease. The sensitivity and specificity of CTC variation for predicting progressive disease were 41% (32-51%) and 80% (73-88%) respectively. CONCLUSION: An early CTC change following therapy does not correlate with RECIST response in patients with advanced cancer enrolled in phase I trials.
Authors: Zhong Ye; Chun Wang; Shaogui Wan; Zhaomei Mu; Zhenchao Zhang; Maysa M Abu-Khalaf; Frederick M Fellin; Daniel P Silver; Manish Neupane; Rebecca J Jaslow; Saveri Bhattacharya; Theodore N Tsangaris; Inna Chervoneva; Adam Berger; Laura Austin; Juan P Palazzo; Ronald E Myers; Neha Pancholy; Darayus Toorkey; Kaelan Yao; Max Krall; Xiuling Li; Xiaobing Chen; Xiuhong Fu; Jinliang Xing; Lifang Hou; Qiang Wei; Bingshan Li; Massimo Cristofanilli; Hushan Yang Journal: Eur J Cancer Date: 2018-12-04 Impact factor: 9.162