Trastuzumab Fails as Adjuvant Therapy in Esophageal Cancer

Preoperative chemoradiotherapy with carboplatin and paclitaxel followed by surgery is the standard treatment for locally advanced esophageal adenocarcinoma. Targeting HER2-positive advanced esophagogastric adenocarcinoma with trastuzumab in the first- and second- or later-line settings has shown success, and a number of other promising agents are in development.

Investigators report an industry-supported, open-label, randomized, phase 3 trial evaluating the addition of trastuzumab to preoperative chemoradiotherapy in patients with HER2-positive esophageal or gastroesophageal junction adenocarcinoma. Patients with clinical T2–3 N0–1 disease testing positive for HER2 by immunohistochemistry or fluorescence in-situ hybridization were randomized to treatment with standard weekly paclitaxel, carboplatin, and 50.4 Gy of radiotherapy followed by surgery, or to the same treatment plus weekly trastuzumab during chemoradiotherapy, an additional dose of trastuzumab prior to surgery, and trastuzumab every 3 weeks for 13 cycles after surgery. Of 194 patients enrolled, most were men (84%) with T3 (79%) or node-positive disease (71%).

Median disease-free survival, the primary endpoint, did not differ between patients treated with or without trastuzumab (19.6 and 14.2 months; hazard ratio, 0.99; P=0.97), and estimated 2-, 3-, and 4-year DFS also did not differ. Similarly, median overall survival (38.5 and 38.9 months; HR, 1.04; P=0.85) and estimated 2-, 3-, and 4-year OS did not differ between groups. There was no difference in surgical outcomes, with similar rates of surgery (84% and 81%), achievement of R0 resection (98% and 100%), and pathologic complete response (27% and 29%). There were no new safety signals.