ArticlesBevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial
Introduction
Metastatic colorectal cancer, as with many cancers, is mainly a disease of elderly people. The median age at diagnosis of colorectal cancer is about 69 years, and roughly 61% of patients are diagnosed at age 65 years or older.1 Risks associated with old age should be taken into account when treatment options are considered, since elderly patients are more likely than younger patients to present with age-related decline in organ function and comorbidities at diagnosis.2, 3 Despite the prevalence of colorectal cancer in the elderly population, such patients are often excluded from randomised trials or represent a minority of enrolled patients.4 As a result, additional data about appropriate treatment options for elderly patients are needed.
Bevacizumab, a humanised monoclonal antibody against VEGF-A, improves progression-free and overall survival when added to chemotherapy in first-line and second-line treatment settings and when continued beyond first progression in metastatic colorectal cancer.5, 6, 7, 8 Subgroup and pooled analyses from randomised trials, along with data from large observational cohort studies, have suggested that the survival benefits associated with the use of bevacizumab in first-line treatment are similar in elderly patients and in the general population.4, 9, 10, 11, 12, 13, 14, 15, 16
International guidelines recommend fluorouracil or capecitabine with or without bevacizumab as first-line treatment for patients with metastatic colorectal cancer for whom more intensive treatment is not appropriate.17, 18 Although these recommendations are supported by data from randomised trials of bevacizumab, these studies did not exclusively enrol a defined elderly patient population.19, 20 Results of phase 2 studies21, 22 have suggested the feasibility and potential efficacy of bevacizumab with capecitabine in patients with metastatic colorectal cancer who are aged 70 years and older.
Despite clinical evidence in the general population of patients with metastatic colorectal cancer, the absence of specific data from randomised trials and the perception of increased toxic effects in elderly patients with comorbidities have led to reservations about treating elderly people with bevacizumab plus chemotherapy.23 We aimed to assess the efficacy and safety of bevacizumab in combination with capecitabine in an exclusively elderly patient population with metastatic colorectal cancer.
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Study design and participants
AVEX (AVastin in the Elderly with Xeloda) is a randomised, open-label, international, phase 3 trial of capecitabine with or without bevacizumab in elderly patients with metastatic colorectal cancer. Participants were recruited from 40 study sites across ten countries (Austria, Canada, Hungary, Italy, Mexico, Poland, Slovenia, South Korea, Spain, and the UK; appendix). Eligible patients were aged 70 years or older and had histologically or cytologically confirmed carcinoma of the colon, rectum,
Results
280 patients were enrolled between July 9, 2007, and Dec 14, 2010. Efficacy analyses used a clinical cutoff date of Jan 19, 2012, giving median follow-ups of 24·8 months (IQR 15·1–37·7) for the bevacizumab plus capecitabine group and 21·6 months (12·8–31·9) for the capecitabine-only group. Final safety analyses used a cutoff date of March 8, 2013, giving median follow-ups of 34·4 months (23·9–48·5) and 29·2 months (25·5–42·4), respectively. The intention-to-treat population consisted of 280
Discussion
Our results show that the addition of bevacizumab to capecitabine significantly improved progression-free survival in elderly patients with metastatic colorectal cancer (panel), with a safety profile consistent with that reported by other studies of bevacizumab plus capecitabine in metastatic colorectal cancer.
Overall survival did not differ significantly between the treatment groups. However, the study was not sufficiently powered to detect differences in overall survival. The use of
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