{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:19:11Z","timestamp":1780589951995,"version":"3.54.1"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"University of North Carolina Lineberger Comprehensive Cancer Center acting as sponsor"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K08 CA259342-02 to A.S. Somasundaram"],"award-info":[{"award-number":["K08 CA259342-02 to A.S. Somasundaram"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Standard therapy for patients with KRAS\/NRAS\/BRAF wild-type (WT), microsatellite stable (MSS), L-sided metastatic colorectal cancer (mCRC) often includes chemotherapy with a monoclonal antibody (mAb) that targets epidermal growth factor receptor (EGFR) such as cetuximab. Preclinical studies suggest the role of CDK4\/6 activity downstream of EGFR as a possible resistance mechanism to anti-EGFR therapy. Therefore, we hypothesized that the addition of the CDK4\/6 inhibitor palbociclib would increase the disease control rate of patients with anti-EGFR na\u00efve KRAS\/NRAS\/BRAF-WT mCRC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>LCCC1717 was a phase II trial with a Simon two-stage design in which patients with KRAS\/NRAS WT mCRC having progressed on at least two lines of therapy were given palbociclib and cetuximab. The primary end point was four-month disease control rate (DCR). Secondary endpoints were overall survival (OS) and progression-free survival (PFS). If six or more patients achieved disease control at four months, the study would continue enrollment, otherwise the study would be discontinued.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 12 subjects were enrolled, 11 of whom had left-sided colon cancer. The four-month DCR was 41.7% (95% CI 15% to 72%) with median OS at 13.9\u2009months and median PFS of 5.3\u2009months, which did not meet the pre-specified endpoint of efficacy. The treatment combination was well tolerated with the most common treatment-related toxicity being decreased lymphocyte and neutrophil counts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>While clinical benefit was observed with the combination, it did not meet its pre-specified endpoint for efficacy in patients with KRAS\/NRAS\/BRAF WT EGFR therapy-na\u00efve mCRC patients. Clinicaltrials.gov Identifier: NCT03446157.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf305","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T14:06:22Z","timestamp":1758722782000},"source":"Crossref","is-referenced-by-count":1,"title":["Phase II single-arm study of palbociclib and cetuximab in anti-EGFR na\u00efve patients with KRAS\/NRAS\/BRAF wild-type, metastatic colorectal cancer"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-720X","authenticated-orcid":false,"given":"Jonathan D","family":"Sorah","sequence":"first","affiliation":[{"name":"Division of Oncology, Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center , Chapel Hill, NC 27599,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic T","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center , Chapel Hill, NC 27599,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Reilley","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Virginia , Charlottesville, VA 22903,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed E","family":"Salem","sequence":"additional","affiliation":[{"name":"Levine Cancer Institute , Charlotte, NC 28204,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Triglianos","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center , Chapel Hill, NC 27599,","place":["United 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