Perioperative docetaxel, cisplatin, and 5-fluorouracil compared to standard chemotherapy for resectable gastroesophageal adenocarcinoma

Abstract

Background

Even though the perioperative chemotherapy improves the overall survival (OS) compared to surgery alone in patients with a resectable gastroesophageal adenocarcinoma (GEA), prognosis of these patients remains poor. Docetaxel (D), cisplatin (C), and 5-fluorouracil (F) regimen improves OS compared to CF among patients with advanced GEA. We evaluated the potential interest of a perioperative DCF regimen, compared to standard (S) regimens, in resectable GEA patients.

Methods

We identified 459 patients treated with preoperative DCF or S regimens. The primary endpoint was OS. Propensity scores were estimated with a logistic regression model in which all baseline covariates were included. We then used two methods to take PS into account and thus make DCF and S patients comparable. OS analyses were performed with Kaplan–Meier and Cox models in propensity score matched samples, and inverse probability of treatment weighted (IPTW) samples.

Results

In the propensity score matched sample, the p-value from the log rank test for OS was 0.0961, and the 3-year OS rate was 73% and 55% in DCF and S groups, respectively. The multivariate Cox regression underlined a Hazard Ratio of 0.55 (95% CI 0.27–1.13) for DCF patients compared to S patients. The results from IPTW analyses showed that DCF was significantly and independently associated with OS (HR = 0.52; 95% CI 0.40–0.69).

Conclusions

In this retrospective multicenter, hypothesis-generating study, the propensity score analyses underlined encouraging results in favor of DCF compared to S regimens regarding OS. This promising result should be validated in a phase-3 trial.

Introduction

Perioperative chemotherapy became standard of care in resectable gastroesophageal adenocarcinoma (GEA) patients since a significant increase in median overall survival (OS) was demonstrated over surgery alone. First, in the MAGIC trial, perioperative treatment with epirubicin (E), cisplatin (C), and 5-fluorouracil (F), provided an improved OS with a Hazard Ratio (HR) of 0.75 compared with surgery alone.¹ More recently, in the FFCD 9705 trial assessing the interest of perioperative CF regimen, the HR for death was 0.69 compared to surgery.² Despite these positive results, the long-term outcomes remain dismal, with less than 40% of patients alive at 5 years.1, 2 Hence, the development of a better treatment strategy in this setting is needed.

We live in an era of targeted therapies and immunotherapies, hence, room for a new chemotherapy agent remains uncertain in perioperative setting. Docetaxel, a potent microtubule-stabilizing agent, has demonstrated antitumor activity in advanced GEA.3, 4 Beyond the first line of chemotherapy, docetaxel in monotherapy improved OS and health related Quality of life (QoL) as compared to best supportive care alone.⁴ In the first line setting, the addition of docetaxel to CF (DCF) demonstrated a better significant benefit for OS and a two-year survival rate over CF.³ QoL assessed by global health status of QLQ-C30 and EQ-5D was also significantly improved in the DCF arm.⁵ In a preoperative setting, encouraging results were observed with the same DCF regimen in a phase II trial. In this study, surgery was performed in 95% of patients and the complete resection (R0) was achieved in all patients, with a pathological complete response rate (pCR) of 9%. No treatment-related or surgical mortality was observed in this study.⁶ A combined multicenter analysis of several modified DCF regimens revealed high histopathological response rates, and the pCR was found to be associated with better survival.⁷

To evaluate the potential interest of docetaxel before its further development in perioperative setting, we performed a retrospective multicenter study in real life to compare the DCF regimen with other chemotherapy regimens.