Phase II Single-Arm Study of Palbociclib and Cetuximab Rechallenge in Patients with KRAS/NRAS/BRAF Wild-Type Colorectal Cancer.

Autor:	Sorah JD; Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Moore DT; Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Reilley MJ; Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA., Salem ME; Levine Cancer Institute, Charlotte, NC, USA., Triglianos T; Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Sanoff HK; Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., McRee AJ; The Janssen Pharmaceutical Companies of Johnson & Johnson, Raritan, NJ, USA., Lee MS; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jazyk:	angličtina
Zdroj:	The oncologist [Oncologist] 2022 Dec 09; Vol. 27 (12), pp. 1006-e930.
DOI:	10.1093/oncolo/oyac222
Abstrakt:	Background: Cetuximab is often administered to patients with KRAS wild-type (KRAS-WT) metastatic colorectal cancer (mCRC), although resistance inevitably develops. We hypothesized that co-inhibition of the epidermal growth factor receptor (EGFR) with cetuximab and downstream cyclin-dependent kinases (CDK) 4/6 with palbociclib would be effective for anti-EGFR rechallenge in KRAS-WT mCRC. Methods: We designed a single-arm, Simon's 2-stage, phase II trial of cetuximab and palbociclib in KRAS-WT mCRC treated with ≥2 prior lines of therapy. We report here on cohort B rechallenging patients with anti-EGFR-based therapy who had disease control of at least 4 months on prior anti-EGFR therapy. Primary endpoint was disease control rate (DCR) at 4 months. Results: Ten evaluable patients were enrolled in this cohort. The 4-month DCR was 20%, which did not fulfill the prespecified 4-month DCR rate to continue. Median progression-free survival was 1.8 months and median overall survival was 6.6 months. Three patients had stable disease, although overall response rate was 0%. Most common treatment-related grades 3-4 adverse events were lymphopenia and leukopenia. Conclusion: Selection of patients for anti-EGFR rechallenge using clinical criteria alone was insufficient to identify response to palbociclib + cetuximab. Additional biomarkers are needed to select anti-EGFR rechallenge and circulating tumor DNA (ctDNA) analysis is planned for samples collected in this study. (ClinicalTrials.gov Identifier: NCT03446157). (© The Author(s) 2022. Published by Oxford University Press.)
Databáze:	MEDLINE
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