Cetuximab plus irinotecan administered biweekly with reduced infusion time to heavily pretreated patients with metastatic colorectal cancer and related RAS and BRAF mutation status
| Autor: | Dorte Linnemann, Julia S. Johansen, Kristin Skougaard, Dorte Nielsen, Jakob V. Schou, Mette Karen Yilmaz, Per Pfeiffer, Finn Ole Larsen, Benny V. Jensen, Estrid Høgdall, Helle Hjorth Johannesen |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
medicine.medical_specialty Colorectal cancer Population Neutropenia medicine.disease_cause Gastroenterology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine education Prospective cohort study neoplasms education.field_of_study Cetuximab business.industry medicine.disease Rash digestive system diseases Irinotecan Oncology 030220 oncology & carcinogenesis KRAS medicine.symptom business medicine.drug |
| Zdroj: | International Journal of Cancer. 148:2542-2556 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.33448 |
| Popis: | Metastatic colorectal cancer (mCRC) is treated with cetuximab 250 mg/m2 administered weekly over 1 hour or biweekly (q2w) over 3.5 hours when combined with irinotecan. This prospective study investigated cetuximab 500 mg/m2 plus irinotecan 180 mg/m2 administered q2w over 1.5 hours independent of RAS or BRAF mutation status in mCRC patients in a third-line setting. The intention-to-treat population included 181 patients. No patients had complete response, 18% had partial responses (PR) and 48% stable disease (SD). For cetuximab, a relative dose intensity of ≥90% was reached in 78% and for irinotecan in 67% of the patients. Grade 3 to 4 toxicities were pain (17%), fatigue (9%), neutropenia (8%), diarrhea (8%), rash (8%), infection (7%) and hypersensitivity (3%). No deaths occurred. Next-generation sequencing in 96.7% of the patients revealed that 50.3% had RAS and BRAFV600E wild type (WT), with a mutation type (MT) in 45.1% of the RAS and 4.4% of the BRAFV600E genes. In patients with RAS-WT and RAS-MT tumors, a PR was obtained in 32% and 4% (P = .000003) and an SD in 43% and 53%, respectively, with a superior PFS (6.2 vs 3.7 months; hazard ratio [HR] 2.12, P = .00001) and OS (12.9 vs 8.8 months; HR 1.71, P = .0008). Treatment efficacy was poor in 7.4% of patients with an RAS mutation outside KRAS exon 2 and in 38% of patients with KRAS exon 2 mutations. Administration of cetuximab and irinotecan q2w, shortening treatment time from 3.5 to 1.5 hours, is recommended as standard therapy. |
| Databáze: | OpenAIRE |
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