{"doi":"10.1093/oncolo/oyaf305","title":"Phase II single-arm study of palbociclib and cetuximab in anti-EGFR naïve patients with KRAS/NRAS/BRAF wild-type, metastatic colorectal cancer","abstract":"BACKGROUND: 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 naïve KRAS/NRAS/BRAF-WT mCRC. METHODS: 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. RESULTS: 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 months and median PFS of 5.3 months, 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. CONCLUSION: 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-naïve mCRC patients. Clinicaltrials.gov Identifier: NCT03446157.","journal":"The Oncologist","year":2025,"id":547106,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03446157"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":589930,"name":"Dominic T. Moore","orcid":null,"position":1,"is_corresponding":false},{"id":1040057,"name":"Matthew J. Reilley","orcid":"0000-0002-4725-0459","position":2,"is_corresponding":false},{"id":254334,"name":"Mohamed E. Salem","orcid":"0000-0002-3661-6785","position":3,"is_corresponding":false},{"id":585206,"name":"Tammy Triglianos","orcid":null,"position":4,"is_corresponding":false},{"id":1439125,"name":"Autumn J McRee","orcid":"0000-0003-2868-1576","position":5,"is_corresponding":false},{"id":590666,"name":"Michael S. Lee","orcid":"0000-0001-8407-3423","position":6,"is_corresponding":false},{"id":445404,"name":"Hanna K. Sanoff","orcid":"0000-0001-8679-4486","position":7,"is_corresponding":false},{"id":258579,"name":"Ashwin Somasundaram","orcid":"0000-0003-3167-406X","position":8,"is_corresponding":false},{"id":1439124,"name":"Jonathan D Sorah","orcid":"0000-0002-2501-720X","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-19T02:53:36.567932Z","pmid":"40990835","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}