{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:12:06Z","timestamp":1790327526015,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Mutant subclones driving anti\u2010EGFR resistance may progressively decline after therapy cessation, potentially reversing resistance to EGFR\u2010targeted treatment. We therefore examined whether rechallenge with cetuximab plus irinotecan is active and tolerable in patients selected by circulating tumour DNA (ctDNA) testing, focusing on metastatic colorectal cancer (mCRC) with\n                      <jats:italic>RAS\/BRAF<\/jats:italic>\n                      wild\u2010type (WT) status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This single\u2010arm, Phase II clinical trial enrolled patients between November 2019 and February 2025. Eligible patients had histologically confirmed\n                      <jats:italic>RAS\/BRAF<\/jats:italic>\n                      WT mCRC at diagnosis, prior cetuximab\u2010based first\u2010line therapy with clinical benefit, radiographic progression while on cetuximab or within 3 months after stopping it, subsequent progression after at least 1 additional systemic therapy, a cetuximab washout period of at least 4 months, and ctDNA\u2010confirmed\n                      <jats:italic>RAS\/BRAF<\/jats:italic>\n                      WT status before rechallenge. Each 2\u2010week cycle delivered intravenous cetuximab (500\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) together with irinotecan (180\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ). The primary endpoint was the objective response rate (ORR). We additionally assessed progression\u2010free survival (PFS), overall survival (OS), and treatment\u2010related adverse events (TRAEs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This study enrolled 36 patients. Partial response was seen in 6 patients (16.7%), stable disease in 10 (27.8%), and progressive disease in 16 (44.4%); the remaining 4 patients were unevaluable due to early loss to follow\u2010up. The ORR reached 16.7% (95% CI: 7.9\u201331.9), with a disease control rate of 44.4% (95% CI: 29.5\u201360.4). The median PFS and OS were 3.9 months (95% CI: 3.1\u20134.7) and 13.0 months (95% CI: 8.1\u201317.9). Multivariate Cox regression analyses identified screening time interval (STI) as an independent predictor of PFS (HR\u00a0=\u00a00.93 per additional month; 95% CI: 0.88\u20130.99). TRAEs of grade 3\u20134 were uncommon and clinically manageable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings suggest that ctDNA\u2010guided rechallenge with cetuximab plus irinotecan may offer benefit in\n                      <jats:italic>RAS\/BRAF<\/jats:italic>\n                      WT mCRC, with STI potentially informing patient selection. Nevertheless, further validation in larger randomised trials is warranted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov Identifier: NCT04224415.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Headlights<\/jats:title>\n                    <jats:p>\n                      <jats:list>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>RAS\/BRAF<\/jats:italic>\n                            wild\u2010type status confirmed by ctDNA may identify candidates for cetuximab rechallenge.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>A longer screening time interval was associated with improved progression\u2010free survival.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These hypothesis\u2010generating findings warrant validation in larger randomised trials.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70827","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:37:51Z","timestamp":1789115871000},"source":"Crossref","is-referenced-by-count":0,"title":["Circulating tumour DNA to guide rechallenge with cetuximab plus irinotecan in\n                    <i>RAS\/BRAF<\/i>\n                    wild\u2010type metastatic colorectal cancer: A nonrandomised clinical trial"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9657-4380","authenticated-orcid":false,"given":"De\u2010Shen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Chuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou Guangdong P. R. 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