title: Circulating tumor cells as a longitudinal biomarker in patients with advanced chemorefractory, RAS-BRAF wild-type colorectal cancer receiving cetuximab or panitumumab.
abstract: A still relevant number of patients with RAS-BRAF wild-type colorectal cancer (CRC) do not respond to treatment with antiepidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab, suggesting that additional biomarkers to guide patient selection are urgently needed. Circulating tumor cells (CTCs) may represent such a biomarker. In this prospective study, 38 patients with advanced RAS-BRAF-wild-type CRC received third-line therapy with cetuximab-irinotecan or panitumumab. Peripheral blood samples for CTC status determination were collected at baseline, during treatment at early (2-4 weeks) and at later (8-10 weeks) times. CTC enrichment was done with the AdnaTest ColonCancerSelect kit, whereas CTC detection was done with the AdnaTest ColonCancerDetect kit. CTC status positivity was defined according to the kit manufacturer's thresholds. Fifty percent of patients were defined as CTC positive at baseline and the overall RECIST response rate was 26%. CTC baseline status was not associated with treatment response, whereas early CTC status and CTC status changes during treatment were significantly associated with tumor response. Kaplan-Meier analysis showed a significantly shorter progression-free survival (median, 2.0 versus 4.0 months, p = 0.004) and overall survival (4.7 versus11.4, p = 0.039) in patients with early CTC + status compared with CTC - ones. In multivariable analysis including classical prognostic factors, the CTC status changes profile during treatment was an independent predictor of both progression-free survival (p < 0.001) and overall-survival (p = 0.001). CTC status assessed early during treatment with anti-EGFR monoclonal antibodies may predict treatment failure in advance compared to imaging-based tools.
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Musella
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Di Buduo
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Martinetti
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sottotetti
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bossi
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Maggi
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy.
authors.forename: Vera
authors.initials: V
authors.lastname: Cappelletti
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D000077544:Panitumumab; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077544:Panitumumab; D000077146:Irinotecan; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin
keywords: biomarker; cetuximab; circulating tumor cell; colorectal cancer; panitumumab