RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment With Anti-EGFR Antibodies in Patients With Metastatic Colorectal Cancer
| Autor: | Michio Nakamura, Fumiyo Maeda, Masahiro Ishizaki, Hideyuki Yanagisawa, Takayuki Yoshino, Masashi Fujii, Masato Nakamura, Masaki Kitazono, Yasuyuki Kawamoto, Akihito Tsuji, Hisatsugu Ohori, Tomoko Sonezaki, Hironaga Satake, Chihiro Komeno, Hidekazu Kuramochi, Yu Sunakawa, Masato Kataoka, Masahiro Takeuchi, Wataru Ichikawa |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research biology Colorectal cancer business.industry medicine.drug_class medicine.disease Monoclonal antibody 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Growth factor receptor Circulating tumor DNA 030220 oncology & carcinogenesis medicine Cancer research biology.protein In patient Antibody business |
| Zdroj: | JCO Precision Oncology. :898-911 |
| ISSN: | 2473-4284 |
| Popis: | PURPOSE Several trials have evaluated the efficacy of rechallenge treatment with anti–epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with metastatic colorectal cancer (mCRC). A recent trial indicated that RAS status in circulating tumor DNA (ctDNA) may potentially predict patients with RAS wild-type mCRC resistant to anti-EGFR mAb who would benefit from rechallenge treatment, and the findings should be further investigated. MATERIAL AND METHODS We enrolled patients whose plasma samples were collected in prospective phase II trials, the JACCRO CC-08 (n = 36) and CC-09 (n = 25), which evaluated rechallenge chemotherapy with anti-EGFR mAb for KRAS wild-type mCRC. RAS in ctDNA was analyzed at the time points of baseline, 8 weeks, and progression using OncoBEAM RAS CRC kit. RESULTS Sixteen patients were enrolled in this study, with a response rate of 0% and a disease control rate (DCR) of 62.5%. RAS mutations were found at baseline in six patients. The DCR was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation at baseline. Patients with RAS mutation at baseline had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without RAS mutation (median PFS, 2.3 v 4.7 months; hazard ratio [HR], 6.2; P = .013; median OS, 3.8 v 16.0 months; HR, 12.4; P = .0028). Six of 10 patients without RAS mutation at baseline acquired RAS mutations at progression. Postprogression survival after rechallenge treatment was numerically shorter in patients with RAS mutation at progression. CONCLUSION RAS status in ctDNA was significantly associated with clinical outcomes in patients with mCRC receiving rechallenge treatment with anti-EGFR mAb. These findings could support the clinical utility of OncoBEAM RAS CRC kits for anti-EGFR mAb rechallenge in RAS wild-type mCRC. |
| Databáze: | OpenAIRE |
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