Delayed esophageal anastomotic complication and ramucirumab therapy: A case report

Current NCCN guidelines for second-line therapy in recurrent or metastatic esophago-gastric cancers recommend the use of VEGF inhibitors such as ramucirumab. VEGF inhibitors have been shown to be associated with gastrointestinal perforation in clinical trials and late colorectal anastomotic leaks in a few case reports. Here, we present a case of late esophageal anastomotic leak in a patient receiving ramucirumab. Case information was obtained from our institution's electronic medical records. The patient was found to have T4N1M0, poorly differentiated invasive adenocarcinoma and subsequently received neoadjuvant chemoradiation followed by hybrid Ivor-Lewis esophagectomy 6 weeks later. He recovered well with no leak or perioperative complications. The patient had disease progression 9 months postoperatively on CT and PET imaging. Sixteen months after surgery he began paclitaxel and ramucirumab and 16 weeks after ramucirumab initiation, he was found to have an esophago-pulmonary fistula in the region of the anastomosis. Biopsies were negative for recurrence at the anastomosis. He died one week later from progressive pneumonia despite stenting. In conclusion, this is the only known report of delayed esophageal anastomotic complication associated with ramucirumab. VEGF inhibitor therapies such as bevacizumab have been associated with late (greater than 3 months postoperative) colorectal anastomotic complications including fistulas and leaks. Risk factors that have been associated are perioperative radiotherapy and history of early postoperative leak. These findings raise concern whether VEGF inhibitor therapy should be used in post-esophagectomy patients with recurrence if these rare but catastrophic events are likely to be terminal.