A phase II trial of preoperative chemoradiation therapy plus bevacizumab and erlotinib in the treatment of localized esophageal cancer.

Abstract

4108 Background: Neoadjuvant chemoradiation therapy is a standard treatment for localized esophageal cancers. The combination of carboplatin (C), paclitaxel (P), 5-FU and radiation therapy (RT) showed a path CR rate of 38% in a previous phase II study. Overexpression of VEGF and/or EGFR in esophageal cancers is associated with a poor prognosis. Both bevacizumab (B) and erlotinib (E) have antitumor activity in multiple solid tumors and are known radiosensitizers. This phase II study evaluated the combination of carboplatin, paclitaxel, 5-FU, bevacizumab, and erlotinib with RT as preoperative treatment of localized esophageal cancers. Methods: Eligibility included previously untreated stage I, II or III surgical candidates with histologically confirmed cancer of the esophagus or GE junction. The treatment regimen was: C: AUC 5 d 1, 22, P: 200 mg/m2 d 1, 22, 5-FU: 225 mg/m2/d IV C1 d 1-35, B: 15 mg/kg d 1, 22, and E: 100 mg PO d 1-42. RT was 1.8 Gy M-F to a total dose of 45 Gy. Patients were restaged between weeks 9-11 and had surgical resection between weeks 12-14. Results: 62 subjects enrolled, 59 currently available for analysis. Median age 64 (43-76), 54 M: 5F, ECOG PS 0 37 (63%). Adenocarcinoma 56 (95%), SCC 3 (5%). Pretreatment clinical stage: I 1 (2%), II 25 (42%), III 30 (51%). Common grade 3/4 toxicities: neutropenia (46%, 10% fever and neutropenia), mucositis (39%), diarrhea (27%), esophagitis (22%), rash (15%), and fatigue (15%). Other significant AEs: 1 G3 peripheral arterial thrombosis, 2 G4 wound complications. 3 treatment related deaths; 1 GI bleed and 2 post op deaths. 42 (71%) subjects have undergone surgical resection, with 3 still undergoing neo-adjuvant treatment. Path CR = 17 (30%); micro residual disease = 13 (23%); macro residual disease = 8 (14%). Conclusions: This multicenter phase II study of chemotherapy plus B and E with RT shows a path CR rate comparable to historical chemoradiation trials. Toxicity was not significantly increased compared to other neoadjuvant combination regimens for esophageal cancer. Given the potential difficulty to build upon this regimen with added agents, the further development of this regimen for patients with esophageal cancers is limited. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech