Phase II study of panitumumab combined with capecitabine and oxaliplatin as first-line treatment in metastatic colorectal cancer patients: clinical results including extended tumor genotyping

AbstractThis clinical trial assessed the efficacy and toxicity of panitumumab combined with oxaliplatin and capecitabine as first-line treatment inKRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. Patients with exon 2KRAS wild-type mCRC received panitumumab 9  mg/Kg, oxaliplatin 130 mg/m2, and capecitabine 2000  mg/m2 repeated every 3 weeks. The primary endpoint was objective response rate (ORR, minimum 42 responses). We retrospectively assessed mutations in genes implicated in CRC with massively parallel sequencing; ERBB2 and EGFR amplification with fluorescence in situ hybridization, and tumor-infiltrating lymphocyte density. Among 78 patients enrolled, 45 (57.7%) completed 6 cycles. Most common grade 3 –4 toxicities were skin rash (19.2%), diarrhea (18%), and neuropathy (6.4%). Among 5 (6.4%) potentially treatment-related deaths, 2 (2.6%) were characterized toxic. Objective response occurred in 43 (55.1%) of the patients (complete 6.4% and partial response 48.7%; stable 17.9% and progressive dis ease 7.7%), while 3.8% were non-evaluable and 15% discontinued their treatment early. Additional mutations inKRAS/NRAS/BRAF were found in 11/62 assessable (18%) tumors. After 51 months median follow-up, median progression-free (PFS) was 8.1 and overall survival 20.2 months, independently ofKRAS/NRAS/BRAF or PI3K-pathway mutation status. Patients withTP53 mutations (n = 34; 55%), as well as those with left colon primary tumors (n = 66; 85%), had signif...
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research