Phase II study of neoadjuvant FLOT and chemoradiation for trimodality therapy of esophageal/GEJ adenocarcinoma.

466 Background: Recent data support use of perioperative FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) chemotherapy over pre-operative chemoradiation (CRT) for patients with resectable esophageal/GEJ adenocarcinoma with limited studies evaluating combined FLOT/CRT. This prospective phase II study (NCT04028167) evaluated a neoadjuvant approach of FLOT followed by CRT for resectable esophageal/GEJ adenocarcinoma (EAC). Methods: Operable patients with cT1-2 N1-2 or cT3-4N any4 Nany non-metastatic EAC were eligible. Neoadjuvant treatment consisted of FLOT x 3 cycles followed by restaging PET and chemoradiation (41.4 Gy / 23 fractions to the primary site and regional lymphatics with weekly carboplatin/paclitaxel). Adjuvant nivolumab for non-pathologic complete response (pCR) was permitted. The primary endpoint was pCR rate among patients receiving the study regimen and undergoing resection, with secondary endpoints including disease free survival (DFS), overall survival (OS), toxicity, and correlative studies. DFS/OS was measured using the Kaplan Meier (KM) method. Interim results are presented after a planned safety analysis. Results: Since 4/2020, 23 patients with median age of 62 (range 40-73) have enrolled. cT3-4 and cN+ disease was present in 20/23 (87%) and 16/23 (70%) of patients, respectively. FLOT was completed by 21/23 patients (reasons for discontinuation included allergic reaction and G5 sepsis/endocarditis). All 21 patients initiating chemoradiation completed planned treatment and 17/21 underwent resection (2 refused surgery after achieving cCR, 1 died of cardiac arrest, 1 patient is awaiting surgery). A pCR was observed in 5/17 resected patients (29%), with pCR or near pCR observed in 9/17 (53%). The complete response rate (pCR + cCR for patients refusing surgery) was 7/19 (37%). Adjuvant nivolumab was administered in 9 patients. The median follow-up among all patients was 20 months with 2-year DFS and OS estimates of 61% and 73%. The regimen was tolerated with G3+ hematologic, G3+ gastrointestinal, and G3+ other toxicity observed in 39%, 13%, and 22% of patients, respectively. Conclusions: In a locoregionally advanced population, neoadjuvant sequential FLOT followed by CRT was well tolerated with encouraging DFS/OS and a high rate of complete response compared to prior studies. This hybrid platform may enhance both locoregional and distant control and is of interest for expanded evaluation. Clinical trial information: NCT04028167 .