Moving target.

Top Line: Does HER2 targeted therapy improve outcomes in patients with HER2+ esophageal adenocarcinoma receiving neoadjuvant chemoradiation and surgery?

The Study: For metastatic, HER2+ esophageal cancer, the addition of trastuzumab to first-line chemotherapy improves overall survival. In the non-metastatic setting, nivolumab recently gained approval by doubling median disease-free survival (DFS) for those with residual disease after neoadjuvant chemoradiation. RTOG 1010 tested whether the addition of concurrent and maintenance trastuzumab to chemoradiation and surgery for esophageal cancer improved DFS. Among >600 patients with T1N1-2 or T2-3N0-2 esophageal adenocarcinoma and plans for chemoradiation followed by surgery, just over 200 (33%) were HER2+. They were randomized to chemoradiation (carboplatin and paclitaxel with 50.4 Gy in 28 fractions) with or without trastuzumab (concurrent with chemoradiation and then adjuvant x 13 cycles after surgery). At surgery, there was no difference in the pathologic complete response rate with trastuzumab (27% v 29%). Trastuzumab did not significantly improve median DFS (19.6 v 14.2 mo) or OS (38.5 v 38.9 mo). At 2 years, the DFS rate was 41.8% v 40%, and the OS rate was 60.8% v 67.4%.

TBL: The addition of concurrent and adjuvant trastuzumab to neoadjuvant chemoradiation and surgery does not improve response rate or survival outcomes for HER2+ esophageal adenocarcinoma. | Safran, Lancet Oncol 2022

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