The oncologist · 2025
Phase II single-arm study of palbociclib and cetuximab in anti-EGFR naïve patients with KRAS/NRAS/BRAF wild-type, metastatic colorectal cancer.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод пока не подготовлен
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Sorah Jonathan D, Moore Dominic T, Reilley Matthew J, Salem Mohamed E, Triglianos Tammy, McRee Autumn J, Lee Michael S, Sanoff Hanna K, Somasundaram Ashwin S
Аннотация
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.
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.