Over the past 10 years, agents targeting the VEGF system, such as bevacizumab, have become standard components of anticancer therapy in various malignancies. Recently, it has become increasingly evident that prolonged duration of anti-VEGF therapy is needed to optimize the therapeutic effect of this class of agents.
Bevacizumab Beyond Progression
In metastatic colorectal cancer, this notion has led to the recommendation to continue anti-VEGF therapy, in particular bevacizumab, until tumor progression. In addition, preclinical findings and circumstantial evidence from observational cohort studies suggested that patients could benefit from continuation of bevacizumab beyond documented tumor progression in this malignancy. Importantly, while initial evaluations of these observational cohort studies reported a surprisingly large difference between the groups of patients who did or did not continue bevacizumab beyond progression, recent analysis using more sophisticated statistical methods projected a benefit for overall survival expressed as hazard ratio for bevacizumab beyond progression in the range of 0.80.1
Insights in Tumor Biology
This hypothesis has now been confirmed in a prospective phase III trial, which documented a statistically significant survival benefit in patients with metastatic colorectal cancer when bevacizumab was continued from first- into second-line therapy. While the magnitude of the survival benefit observed might have disappointed some believers in the concept of bevacizumab beyond progression, the results provide new insights into tumor biology in general and our understanding of treatment resistance in particular. The inevitable financial implications of these results aside, the data presented at ASCO will hopefully open the door for future innovative and optimized treatment strategies. ■
Disclosure: Dr. Grothey has served as an unpaid advisor or consultant for Bayer.
1. Grothey A, Bekaii-Saabts, Hurwitz H, et al: Cumulative exposure to bevacixumab after progression correlates with increased survival in patients with metastatic colorectal cancer: A time-dependent analysis of the ARIES observational cohort study. European Multidisciplinary Cancer Congress. Abstract 6031. Presented September 25, 2011.
In a study highlighted at a press briefing during the 2012 ASCO Annual Meeting, German investigators reported that prolonging treatment with bevacizumab (Avastin) beyond disease progression extends overall survival in patients with metastatic colorectal cancer.1 Patients received bevacizumab plus...
Invited discussant Alan Venook, MD, of the University of California, San Francisco, pointed out that the hazard ratio of 0.81 and the 1.4-month improvement in overall survival in the TML trial did not reach the target hazard ratio of 0.77 in the statistical design of the study. However, “it is...
Additional noteworthy gastrointestinal cancer studies presented during oral abstract sessions at the 2012 ASCO Annual Meeting included the following trials in metastatic colorectal cancer.
Perifosine/Capecitabine Fails in Phase III Trial
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