Patient-reported outcomes in NRG Oncology RTOG 1010: Phase 3 trial evaluating the addition of trastuzumab to trimodality treatment of HER2 overexpressing esophageal adenocarcinoma

Background: NRG/RTOG 1010 evaluated trastuzumab added to trimodality therapy for HER2+ localized esophageal adenocarcinoma (EAC) management. Secondary PRO objectives assessed improvement in the FACT-Esophageal Cancer Subscale (ECS), version 4, with trastuzumab, and if improved ECS correlated with pathologic complete response (pCR). Methods: Patients were randomized to weekly paclitaxel/carboplatin/radiation (chemoradiation, CRT) followed by surgery ± trastuzumab (CRT + Tras). Disease-free survival (DFS) was the primary end point. The projected PRO sample size of 158 patients, based on an 80% participation rate of the DFS primary endpoint sample size of 197 HER2+ patients, would provide ≥ 89% power to detect ≥25% increase in the proportion of CRT + Tras patients with ECS improvement from baseline to 6–8 weeks post-CRT; one-sided α = 0.05, using a χ² test. Improvement in ECS and its swallowing index (SI) and eating index (EI) was defined as 5-, 2-, and 2-point increases, respectively, from baseline to 6–8 weeks post-CRT. Univariate logistic regression was assessed if pCR was associated with improved ECS. Results: From 2010 to 2015, 203 HER2+ patients were randomized and 194 were eligible. Of 171 PRO consenting patients, the ECS was completed by 162 (95%) at baseline, 108 (64%) 6–8 weeks, 82 (49%) 1 year, and 55 (33%) at 2 years. The proportion of patients with an improvement in 6–8 weeks ECS was higher on the CRT + Tras arm (46% vs. 38%), although not significantly different (p =.39). There was no correlation between pCR and ECS scores at 1 year, with 39% and 37% of pCR and non-pCR patients, respectively, having improved 1-year ECS scores. Conclusions: The addition of trastuzumab to CRT for localized HER2+ EAC did not improve PROs.