LAUSR

Background: Pre-operative chemoradiation (CRT) followed by surgery for localized EGAC leads to a pathologic complete response (pCR) rate of 20%. Achievement of pCR is associated with improved overall survival (OS). Therefore, several studies have used IC before CRT to improve pCR rates but saw mixed results. We used a novel combination of FTD/TPI and oxaliplatin as IC before the standard CRT in localized EGAC with the primary objective of increasing the pCR rate. Methods: We enrolled patients (pts) in this open-label, single-arm, multicenter, phase II trial between Jan 2020 and Oct 2022. Pts with potentially resectable EGAC, adequate organ function, ECOG performance status of 0 -1, age <76 years, and endoscopic ultrasound (EUS)-determined node-positive disease with any T-stage or T3-T4a with any N stage were eligible. Pts received three cycles of IC with FTD/TPI (35 mg/m² BID, days 1-5 every 14 days) and oxaliplatin (85 mg/m² every 14 days on day 1). Pts then underwent concurrent CRT (radiation dose of 5040 cGY) with weekly Carboplatin (AUC 2) and Paclitaxel (50 mg/m2) for 6 weeks, followed by surgery. The primary objective was to evaluate the pCR rate. The secondary objectives were 2-year disease-free survival (DFS), 2-year OS, and toxicities. Using a Simon two-stage design, we enrolled 22 evaluable patients in stage 1 with at least 5 pCRs to proceed to stage 2. We collected blood samples at different time points to measure circulating tumor DNA (Ct DNA) as a correlative endpoint. Clinical trial information: NCT04097028. Results: Of the 22 enrolled pts, 19 (86.4%) were male, and 20 (90.9%) were Caucasian. The median age was 61 years, and 12 (54.5%) had a primary disease at the gastroesophageal junction. Twenty (90.9%) pts had T3 disease, and 15 (68.2%) had node-positive disease by EUS. IC led to a 35% or more reduction in SUVmax in 60% of patients before CRT. At the time of data cutoff, 13 (59.1%) had surgery, 1 (4.5%) was awaiting surgery, 5 (22.7%) had progressive disease during the study, and 3 (13.6%) discontinued the study due to adverse events (AEs). Only 2 pts had pCRs, and an additional 4 had near pCRs. Since we could not meet our pre-defined pCR rate in stage 1, the study was closed due to futility. After a median follow-up of 15.8 months, 2-year OS and DFS were 43% and 41%, respectively. Nine (40.9%) had grade 3 or higher AEs. Nausea (59.1%) and fatigue (59.1%) were the most common treatment-related AEs; these were grade 1-2 events. The most common grade 3 or higher events were neutropenia (13.6%) and lymphopenia (9.1%). No febrile neutropenia was noted. Conclusion: IC with FTD/TPI and oxaliplatin before standard CRT failed to improve pCR in resectable EGAC, although it was reasonably well tolerated and showed activity. Ct DNA analysis is ongoing and will hopefully identify a select subgroup of pts who may benefit from this approach. Citation Format: Sarbajit Mukherjee, Sylvia Alarcon, Christos Fountzilas, Sarah Chatley, Renuka Iyer, Deepak Vadehra, Moshim Kukar, Kristopher Attwood, Anthony George, Alyson Brown, Chih-Yi Liao, Hassan Hatoum, Sagila George. Trifluridine/tipiracil (FTD/TPI) and oxaliplatin as induction chemotherapy (IC) in resectable esophageal and gastroesophageal junction adenocarcinoma (EGAC): Preliminary results from a phase II study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT146.