From studies of bevacizumab in metastatic breast cancer, we have seen a reversal of FDA approval of bevacizumab, due in part to a lack of improvement in OS (16-18). This reversal raised the controversy around the inability to improve OS when powering studies for the primary endpoint of tumor response and PFS rather than OS (19). However, even with a statistically significant positive trial, such as with regorafenib, Inhibitors,research,lifescience,medical the absolute benefit in OS may be outweighed by the cost and toxicity of treatment. Thus, along with efficacy, cost and absolute differences in survival should play a role in the FDA approval of new agents. In our cohort, we did not detect any predictive factors that would identify
patients benefiting from VEGF inhibition. Our analysis showed that K-RAS status and duration of prior bevacizumab therapy did not affect efficacy outcomes. If mCRC patients who would benefit from VEGF inhibition could be identified by predictive biomarkers, treatment would become more efficacious Inhibitors,research,lifescience,medical and cost-effective. Recently, the AVAGAST trial demonstrated that plasma VEGF-A and tumor neuropilin-1 predict clinical outcome in patients with advanced
gastric cancer treated with bevacizumab (20). Inhibitors,research,lifescience,medical For mCRC patients receiving bevacizumab, low levels of baseline angiopoetin-2, a key regulator of vascular remodeling in conjunction with VEGF, has been associated with better survival (21,22). Appropriate predictive biomarkers should be incorporated prospectively into early phase clinical trials in order to identify a subset of mCRC patients who would benefit from VEGF inhibition. Our study is limited by having a heterogeneous population that was not randomized nor controlled between the two comparative Inhibitors,research,lifescience,medical groups; however, this retrospective analysis Inhibitors,research,lifescience,medical demonstrates the need to evaluate new agents in mCRC and to look beyond VEGF inhibition. Acknowledgments Nicole Jaime, MPH for designing the database for data
collection. Subrata Haldar, PhD for help with scientific writing. Disclosure: Devalingam Mahalingam is Advisory Board/buy PF299804 Speaker Bureau for Bayer Pharmaceuticals. The authors declare no conflict of interest.
An otherwise healthy 45-year-old man presented with significant abdominal bloating and tarry stools and was found to have a mass in the third either portion of the duodenum. Computed tomography (CT) scan revealed concentric wall thickening of the distal duodenum and a mildly enlarged aortocaval lymph node. A Whipple procedure was performed and identified a tumor in the third portion of the duodenum. Pathologic examination of the 2.5 cm duodenal mass revealed a moderately to poorly differentiated duodenal adenocarcinoma with focal signet ring features. Metastatic carcinoma was found in three of five periduodenal lymph nodes and one omental implant. Six weeks following surgery, the patient was started on adjuvant chemotherapy with modified FOLFOX6 for eight doses followed by consolidative chemoradiation.