Tracheoesophageal Fistula in a Patient With Advanced NSCLC Who Received Chemoradiotherapy and Ramucirumab
Authors: Paolo B. Abada
Journal: Journal of Thoracic Oncology (2018)

Eli Lilly would like to express thanks to Drs. Yen-Lung Lee, Jui-Feng Hsu, and Chih-Jen Yang for submitting to the Journal of Thoracic Oncology an important case of tracheoesophageal fistula in a patient with advanced NSCLC who received chemoradiotherapy and ramucirumab.1Lee Y.-L. Hsu J.-F. Yang C.-J. Tracheoesophageal fistula in a patient with advanced non-small cell lung cancer who received chemoradiotherapy and ramucirumab.J Thorac Oncol. 2019; 14: e15-e16Google Scholar Lilly would like to respond to this letter and highlight some key points from the Cyramza (ramucirumab) prescribing information which are relevant for this particular case. In Taiwan, Cyramza is currently approved in combination with docetaxel for the treatment of patients with locally advanced or metastatic NSCLC with disease progression on or after platinum-based chemotherapy.2Product index.https://www.lilly.com.tw/cn/product/index.aspxGoogle Scholar The letter to the editor states “Although bevacizumab has been associated with the formation of tracheoesophageal fistulae when combined with chemoradiotherapy, this life-threatening complication has never been reported with ramucirumab, another FDA-approved antiangiogenic agent for the treatment of NSCLC, combined with chemoradiotherapy,” which we believe may misrepresent Cyramza’s approved NSCLC indication. We write to you to clarify this matter and underscore that Cyramza is not indicated for use in combination with docetaxel-cisplatin or as a concurrent treatment with chemoradiotherapy. The exact mechanism of tracheoesophageal fistula formation is unknown. Fistula formation involving gastrointestinal and non-gastrointestinal sites has occurred in patients treated with Cyramza. Risk factors for fistula in Cyramza-treated patients are consistent with the known risk factors in the general patient population and include advanced metastatic cancers, previous surgical procedures, and prior radiotherapy, as well as other underlying medical conditions such as diabetes mellitus and diverticulitis. The letter correctly outlines that local radiation and chronic inflammation are known to be precipitating factors for tracheoesophageal fistula formation. To date, a small number of cases of fistula reported in Cyramza studies and postmarketing safety data do not provide sufficient evidence of causal association of fistula formation and Cyramza. Further, the letter states “Ramucirumab is a recombinant human IgG1 monoclonal antibody that targets vascular endothelial growth factor (VEGF) receptors.” We would like to clarify that the binding of Cyramza is specific to the VEGF 2 receptor. Physicians should refer to the local prescribing information for specific details regarding the approved indication(s), as well as important safety warnings and precautions that should be taken into consideration when prescribing Cyramza. Tracheoesophageal Fistula in a Patient with Advanced Non–Small Cell Lung Cancer Who Received Chemoradiotherapy and RamucirumabJournal of Thoracic OncologyVol. 14Issue 1PreviewAntiangiogenic agents are widely used in combination with chemotherapy for many cancers, including lung cancer. Bevacizumab is approved for the first-line treatment of advanced stage nonsquamous cell lung cancer in combination with platinum-based chemotherapy. Ramucirumab is a recombinant human IgG1 monoclonal antibody that targets vascular endothelial growth factor receptors. The REVEL study enrolled patients with NSCLC, all of whom were refractory to first-line platinum-based chemotherapy. The patients were randomized to receive ramucirumab with docetaxel or docetaxel alone; significantly improved overall survival and progression-free survival rates were noted for the patients who received combination treatment with ramucirumab. Full-Text PDF Open Archive