Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study.
ABSTRACT Bevacizumab significantly improves survival when added to chemotherapy for metastatic colorectal cancer (mCRC). The Bevacizumab Expanded Access Trial (BEAT) evaluated the safety and efficacy of bevacizumab plus first-line chemotherapy in a general cohort of patients with mCRC.
Patients with unresectable mCRC received chemotherapy (physician's choice) plus bevacizumab [5 mg/kg every 2 weeks (5-fluorouracil regimens) or 7.5 mg/kg every 3 weeks (capecitabine regimens)]. The primary end point was safety, including prospective data collection in patients receiving unanticipated surgery during the study. Secondary objectives were progression-free survival (PFS) and overall survival (OS).
The final analysis comprised 1914 assessable patients (male 58%; median age 59 years). Chemotherapy included 5-fluorouracil/leucovorin (5-FU/LV) + oxaliplatin (29%), irinotecan plus 5-FU/LV (26%), capecitabine plus oxaliplatin (18%) and monotherapy (16%). Serious/grade 3-5 adverse events of interest for bevacizumab included bleeding (3%), gastrointestinal perforation (2%), arterial thromboembolism (1%), hypertension (5.3%), proteinuria (1%) and wound-healing complications (1%). Sixty-day mortality was 3%. Median PFS was 10.8 months [95% confidence interval (CI) 10.4-11.3 months] and median OS reached 22.7 months (95% CI 21.7-23.8 months).
The BEAT study shows that the efficacy and safety profile of bevacizumab in routine clinical practice is consistent with results observed in prospective randomised clinical trials and another large observational study in the United States (BRiTE study).
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ABSTRACT: The ability to tailor biologic therapy based on the status of tumor biomarkers and monoclonal antibodies has become very important in the last years. The role of tumor biomarkers in treating colorectal cancer, specifically the K-RAS gene, was identified. K-RAS had a higher interest after Lievre and colleagues reported at the 2008 American Society of Clinical Oncology (ASCO) meeting, their analysis of K-RAS mutations in tumors from patients who did not appear to benefit from cetuximab therapy, providing additional data involving K-RAS mutant tumors and their lack of response to cetuximab, as part of first-line therapy for metastatic colorectal cancer. Furthermore, other trials evaluated the K-RAS status and the first-line treatment of metastatic colorectal cancer, the treatment of refractory metastatic cancer and dual-antibody therapy in the first-line treatment of colorectal cancer. Patients with mutant K-RAS colorectal tumors have no benefit from cetuximab, no matter the type of chemotherapy regimen.Journal of medicine and life 06/2012; 5(2):168-72.
Article: XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer: the boxe study.[show abstract] [hide abstract]
ABSTRACT: PURPOSE: The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (CRC). An increased risk of arterial thromboembolic events has been observed in some trials in older patients, and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated. This phase II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC. METHODS: Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m(2) on day 1, plus capecitabine 1,000 mg/m(2) twice daily on days 1-14, every 3 weeks up to a maximum of 8 cycles. Patients then received maintenance therapy consisting of bevacizumab alone (7.5 mg/kg) once every 3 weeks up to disease progression. The primary study end-points were safety and response rate. RESULTS: A total of 44 patients were recruited. In an intention-to-treat analysis, the overall response rate was 52 % [95 % confidence interval (CI) 37 to 68 %], with 86 % of patients achieving disease control. Median PFS and overall survival were 11.5 months (95 % CI 10.0-12.9 months) and 19.3 months (95 % CI 16.5-22.1 months), respectively. In all, 10 patients (23 %) had grade 3/4 adverse events (AEs), the most common being diarrhea (9 %), neutropenia (7 %), peripheral neuropathy (7 %), and stomatitis (7 %). No patients died because of treatment-related AEs. The rate of bevacizumab-related AEs (hypertension, thromboembolic events, and gastrointestinal perforation) was consistent with that reported earlier in the general CRC population. CONCLUSION: The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC. Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients.Cancer Chemotherapy and Pharmacology 10/2012; · 2.83 Impact Factor