{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:01:11Z","timestamp":1792976471011,"version":"4.5.0"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n The available evidence regarding anti\u2013epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA)\n RAS\/BRAF<\/jats:italic>\n wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA\n RAS\/BRAF<\/jats:italic>\n wt mCRC.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This nonrandomized controlled trial used a pooled analysis of individual patient data from patients with\n RAS\/BRAF<\/jats:italic>\n wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28.1 [25.8-35.0] months).\n <\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Patients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated. Exploratory subgroup analysis evaluating several clinical variables was performed. Safety was reported.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Overall, 114 patients with\n RAS\/BRAF<\/jats:italic>\n wt ctDNA mCRC (median [IQR] age, 61 [29-88] years; 66 men [57.9%]) who received anti-EGFR rechallenge as experimental therapy (48 received cetuximab plus avelumab, 26 received trifluridine-tipiracil plus panitumumab, 13 received irinotecan plus cetuximab, and 27 received panitumumab monotherapy) were included in the current analysis. Eighty-three patients (72.8%) had received 2 previous lines of therapy, and 31 patients (27.2%) had received 3 or more previous lines of therapy. The ORR was 17.5% (20 patients), and the DCR was 72.3% (82 patients). The median PFS was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months). The subgroup of patients without liver involvement had better clinical outcomes. The median PFS was 5.7 months (95% CI, 4.8-6.7 months) in patients without liver metastasis compared with 3.6 months (95% CI, 3.3-3.9 months) in patients with liver metastasis (hazard ratio, 0.56; 95% CI, 0.37-0.83;\n P<\/jats:italic>\n \u2009=\u2009.004). The median OS was 17.7 months (95% CI, 13-22.4 months) in patients without liver metastasis compared with 11.5 months (95% CI, 9.3-13.9 months) in patients with liver metastasis (hazard ratio, 0.63; 95% CI, 0.41-0.97;\n P<\/jats:italic>\n \u2009=\u2009.04). Treatments showed manageable toxic effects.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n These findings suggest that anti-EGFR rechallenge therapy has promising antitumor activity in patients with refractory ctDNA\n RAS\/BRAF<\/jats:italic>\n wt mCRC. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifiers:\n NCT02296203<\/jats:ext-link>\n ;\n NCT04561336<\/jats:ext-link>\n ;\n NCT03227926<\/jats:ext-link>\n ;\n NCT05468892<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.5635","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T11:01:03Z","timestamp":1712660463000},"page":"e245635","source":"Crossref","is-referenced-by-count":61,"title":["Anti-EGFR Rechallenge in Patients With Refractory ctDNA\n RAS\/BRAF<\/i>\n wt Metastatic Colorectal Cancer"],"prefix":"10.1001","volume":"7","author":[{"given":"Davide","family":"Ciardiello","sequence":"first","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy"},{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Troiani","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Mauri","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, Milano, Italy"},{"name":"Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milano, Italy"},{"name":"IFOM ETS\u2013The AIRC Institute of Molecular Oncology, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Rossini","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy"},{"name":"Division of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Famiglietti","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Del Tufo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Masi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy"},{"name":"Division of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, La Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Avallone","sequence":"additional","affiliation":[{"name":"Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori\u2013IRCCS\u2013Fondazione G. 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