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Retreatment With Anti-EGFR Antibodies in Metastatic Colorectal Cancer Patients: A Multi-institutional Analysis
Institution:1. Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy;2. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;3. Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology, IOV-IRCCS, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy;4. Department of Medical Oncology, Campus Bio-Medico, University of Rome, Rome, Italy;5. Fondazione Policlinico Universitario A. Gemelli, IRCCS-UOC Oncologia Medica, Rome, Italy;6. Medical Oncology Department, University Hospital, University of Cagliari, Cagliari, Italy;7. Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy;1. Department of Dermatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan;2. Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;1. Bordeaux PharmacoEpi, INSERM CIC1401, Université de Bordeaux, CHU de Bordeaux, Bordeaux, France;2. Centre Antoine Lacassagne, Nice, France;3. Hepato-billary center, Hôpital Paul Brousse, Villejuif, France;4. Institut Bergonié, Bordeaux, France;5. INSERM U1219, Université de Bordeaux, Bordeaux, France;6. Digestive oncology and Gastroenterology Department, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France;1. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy;2. Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy;3. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;4. Department of Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy;5. Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy;1. David Geffen School of Medicine at UCLA, Santa Monica, CA;2. Rocky Mountain Cancer Centers, Denver, CO;3. Cancer Center of Kansas, Liberal, KS;4. Georgia Cancer Specialists, Atlanta, GA;5. Montefiore Medical Center, Bronx, NY;6. Texas Oncology, Round Rock, TX;7. Amgen Inc, Thousand Oaks, CA;1. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy;2. Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Milano, Italy;3. Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milano, Italy
Abstract:BackgroundOn the basis of retrospective analyses and phase 2 studies, metastatic colorectal cancer patients whose disease responded to a first-line regimen containing an anti–epidermal growth factor receptor (EGFR) agent may experience benefit from anti-EGFR readministration in later therapy lines. While the analysis of circulating tumor DNA seems a promising tool to select the best candidates for this strategy, identifying clinical predictors of anti-EGFR sensitivity would be useful to drive treatment choices in daily practice.Patients and MethodsA real-life database of 5530 patients treated at 6 institutions was queried. Included were patients who were retreated with anti-EGFRs, who had RAS/BRAF wild-type–status tissue samples, who had received a first-line anti-EGFR–based regimen with at least stable disease as best response, and who had received at least one further line of therapy before anti-EGFR retreatment. The association with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of variables potentially related to anti-EGFR sensitivity was investigated.ResultsA total of 86 patients were identified. The ORR during anti-EGFR retreatment was 19.8%; median PFS and OS were 3.8 and 10.2 months, respectively. No significant association of clinical features of anti-EGFR sensitivity with ORR, PFS, and OS was observed. Among the 56 patients with a time from the last anti-EGFR administration to first-line progressive disease of < 3 months (rechallenge group), > 2 prior therapy lines and a longer anti-EGFR–free interval were associated with higher ORR, but not with longer PFS or OS.ConclusionClinical features we deemed surrogates of anti-EGFR sensitivity were not reliable predictors of benefit from anti-EGFR retreatment.
Keywords:Chemorefractory metastatic colorectal cancer  Circulating tumor DNA  Liquid biopsy  Rechallenge  Resistance and sensitivity to anti-EGFR
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