Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction Adenocarcinoma: A Phase II Study

TL;DR

A new chemotherapy combination before standard treatment for esophageal cancer did not improve outcomes, but ctDNA clearance was linked to better survival.

Contribution

Evaluated a novel induction chemotherapy regimen with trifluridine/tipiracil and oxaliplatin in resectable EGAC.

Findings

Only 2 out of 22 patients achieved a pathologic complete response.

ctDNA clearance correlated with significantly higher overall and progression-free survival.

The regimen was associated with common adverse events like nausea and fatigue.

Abstract

Preoperative chemoradiation (CRT) followed by surgery for localized esophageal and gastroesophageal junction adenocarcinoma (EGAC) is a standard of care with a pathologic complete response (pCR) rate of 20%. We evaluated a novel combination of trifluridine/tipiracil with oxaliplatin as induction chemotherapy (IC) followed by CRT.

We enrolled patients with potentially resectable localized EGAC (T3, T4aN0, or node‐positive disease) in this open‐label, single‐arm, multicenter, Phase II trial between January 2020 and October 2022. Patients received three cycles of IC with trifluridine/tipiracil and oxaliplatin and then underwent concurrent CRT with weekly carboplatin and paclitaxel followed by surgery. The primary objective was to evaluate the pCR rate. The secondary objectives were to evaluate 2‐year progression‐free survival (PFS), 2‐year overall survival (OS), and toxicities. Circulating tumor DNA (ctDNA) was measured at prespecified intervals to assess its correlation with clinical outcomes.

Of the 22 enrolled patients, 19 (86.4%) were male and 20 (90.9%) were Caucasian. The median age was 61 years, and 12 (54.5%) had their primary disease at the gastroesophageal junction. Twenty (90.9%) patients had T3 disease, and 15 (68.2%) had node‐positive disease. Only two patients had pCRs, and an additional five had near pCRs. Since we could not meet our predefined pCR rate at the interim analysis, the study was closed. After a median follow‐up of 15.8 months, 2‐year OS and PFS were 43% and 41%, respectively. ctDNA clearance was associated with a significantly higher OS rate (p = 0.012) and PFS rate (p = 0.008). Nausea (59.1%) and fatigue (59.1%) were common treatment‐related adverse events (AEs); nine (40.9%) patients had Grade 3 or higher AEs.

IC with trifluridine/tipiracil and oxaliplatin followed by CRT did not improve pCR rate in resectable EGAC compared to pCR from previous reports with CRT alone. We found a correlation between ctDNA clearance and improved survival, which merits further investigation.

NCT04097028.

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