Esophageal adenocarcinoma (EAC) is a malignancy with rising incidence in Western countries, largely due to increasing rates of gastroesophageal reflux disease and obesity. Despite advancements in treatment, the prognosis for EAC remains poor, with a five-year survival rate of less than 20% for advanced stages. Current management of locally advanced, resectable EAC often involves neoadjuvant chemoradiation therapy, such as the CROSS regimen (carboplatin/paclitaxel with 41.4Gy radiation) followed by surgery. However, the optimal multimodal approach remains under debate, with growing interest in perioperative chemotherapy as a potentially superior alternative. The ESOPEC trial, presented at ASCO 2024, provides pivotal data comparing these two strategies, aiming to improve patient outcomes in EAC.
Background of the ESOPEC Trial
The ESOPEC trial (NCT02509286) is a multicenter prospective randomized study conducted in Germany, aimed at determining whether neoadjuvant chemoradiation (CROSS regimen) or perioperative chemotherapy (FLOT regimen) is superior for the curative treatment of resectable EAC. The primary endpoint of the study was overall survival (OS), with a target hazard ratio (HR) of 0.645 to achieve 90% power.
Study Design and Method
Eligible patients had resectable EAC with clinical staging of cT1 cN+ cM0 or cT2-4a cNany cM0. They were randomly assigned to one of two treatment arms:
- CROSS regimen: 41.4Gy radiation plus carboplatin/paclitaxel, followed by surgery.
- FLOT regimen: 5-FU/leucovorin/oxaliplatin/docetaxel, given perioperatively and followed by surgery.
The study involved 438 patients from 25 sites in Germany, with the analysis conducted by intention-to-treat. Key variables included study site, N stage, and age.
Results of the ESOPEC Trial
The trial’s results provide crucial insights:
- Patient Characteristics: The baseline characteristics were well balanced between the FLOT (221 patients) and CROSS (217 patients) arms, with a median age of 63 years and a predominance of male patients (89.3%).
- Treatment and Surgery: Neoadjuvant treatment was initiated in 403 patients, and surgery was performed in 371 patients. The R0 resection rate was 80.1%, slightly favoring the FLOT arm.
- Survival Outcomes: After a median follow-up of 55 months, 218 patients had died (97 FLOT; 121 CROSS). The median OS was significantly longer in the FLOT arm at 66 months compared to 37 months in the CROSS arm. The 3-year OS rates were 57.4% for FLOT and 50.7% for CROSS.
- Pathological Response: Among the 359 patients with available tumor regression data, the FLOT arm had a higher pathological complete response rate (19.3%) compared to the CROSS arm (13.5%).
Implications for Clinical Practice
The ESOPEC trial demonstrates that perioperative FLOT chemotherapy significantly improves survival compared to neoadjuvant CROSS chemoradiation in patients with resectable EAC. These findings suggest that FLOT should be considered the preferred treatment strategy for eligible patients.
For Patients and Caregivers:
- Informed Decisions: Understanding these treatment options can help in making informed decisions about care. Discussing the potential benefits and risks of each regimen with healthcare providers is crucial.
- Hope and Optimism: The improved survival rates associated with FLOT offer hope and a more optimistic outlook for patients facing EAC.
For Healthcare Providers:
- Treatment Selection: Incorporating FLOT into treatment protocols may enhance patient outcomes. Providers should stay informed about the latest clinical trial results to offer the best care options.
- Holistic Care: Considering both the survival benefits and quality of life impacts when choosing treatment modalities is essential for holistic patient care.
The ESOPEC trial provides compelling evidence that perioperative FLOT chemotherapy is superior to neoadjuvant CROSS chemoradiation for treating resectable locally advanced EAC. These findings will likely influence future treatment guidelines and practices, offering new hope for patients battling this challenging disease.
Staying updated on such pivotal research ensures that patients receive the most effective and cutting-edge care available. For those affected by EAC, the advancements in treatment strategies presented in the ESOPEC trial bring renewed optimism and clearer paths to improved survival and quality of life.
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.