Patient-Reported Outcomes (PROs) in NRG Oncology RTOG 1010: Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2 Overexpressing (HER2+) Esophageal Adenocarcinoma (EAC)
Kachnic LA, Moughan J, Hong TS, Haddock MG, Tahir N, Yoon HH, Pardo DAD, Anderson CM, Seaward SA, Lominska C, O'Brien P, Katz AW, Salo J, Christie AD, Dorth JA, Aljumaily R, Gore EM, Safyan HP, and Movsas B. Patient-Reported Outcomes (PROs) in NRG Oncology RTOG 1010: Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2 Overexpressing (HER2+) Esophageal Adenocarcinoma (EAC). Int J Radiat Oncol Biol Phys 2022; 114(3):S14.
Int J Radiat Oncol Biol Phys
Purpose/Objective(s): NRG/RTOG 1010 evaluated the benefit of trastuzumab for patients (pts) with HER2+ localized EAC receiving trimodality therapy. Adding trastuzumab did not improve disease-free (primary endpoint) or overall survival, nor treatment toxicity (Lancet Oncology 2022). The primary PRO objective was improvement (impr) in the FACT-Esophageal Cancer Subscale (ECS) score with trastuzumab at restaging prior to surgery. A secondary objective was to assess if impr in ECS score is associated with pathologic complete response (pCR).
Materials/Methods: Pts with HER2+ EAC (T1N1-2; T2-3N0-2) were stratified by presence of adenopathy & randomized 1:1 to weekly paclitaxel, carboplatin with 50.4 Gy radiation (CRT) followed by surgery ± trastuzumab (CRT+T), 4mg/kg week 1, 2mg/kg/weekly x 5 during CRT, 6 mg/kg x1 prior to surgery, and then 6mg/kg every 3 weeks (wks) x 13. The ECS, v4, was done at baseline, 6-8 wks post-CRT and at 1 & 2 years. Impr in ECS and its Swallowing Index (SI) & Eating Index (EI) were defined as increases of 5, 2 & 2 points, respectively, from baseline. PRO sample size provided ≥ 80% power with 1-sided 0.05 alpha & a chi-squared test to determine if the proportion of pts categorized as improved at 6-8 wks is ≥ 25% higher for the CRT+T arm. Correlation between pCR & impr in ECS score was evaluated via chi-squared test.
Results: From 2010-2015, 203 HER2+ pts were randomized; 194 eligible. Of 171 PRO consenting pts, the ECS was completed by 162 (95%) at baseline, 108 (64%) 6-8 wks, 82 (49%) 1 year & 55 (33%) at 2 years. The main reason for FACT-E noncompliance was pt death. Patient & tumor characteristics were similar between arms. Median age was 63 years; 86% male; 96% white; 65% Zubrod 0, 80% cT3 & 71% cN1-2 (AJCC 7th ed). For ECS scores at 6-8 wks, the mean change (Δ) was higher (better) from baseline at 4.6 (95% CI: 1.3, 7.8) for the CRT+T arm vs 0.9 (95% CI: -2.7, 4.6) for the CRT arm; the proportion of pts with an impr in 6-8 wks ECS was higher on the CRT+T arm (46% vs 38% on the CRT arm) although not significantly different (p=0.39). Table 1 shows ECS, SI & EI scores for all timepoints. At 6-8 wks, 30% with a pCR had an impr in ECS vs 45% of nonpCR pts (p=0.18). There were no significant correlations between pCR and ECS, SI & EI impr at any time points.
Conclusion: The addition of trastuzumab to trimodality therapy for localized HER2+ EAC did not significantly improve survival or PROs. ECS score improvement following therapy was not associated with a pCR. The higher proportion of pts with improved ECS at 6-8 weeks and 2 years in the CRT+T arm is interesting and suggests that HER2 may still be an important target to explore.