Dr Kim Discusses Results from the ESOPEC Trial in Esophageal Carcinoma
Presenter
Richard Kim, MD, Moffitt Cancer Center
Conference
2024 ASCO Direct™ Philadelphia
The Bottom Line
The ESOPEC trial evaluated two treatment approaches for patients with surgically treatable (resectable) esophageal adenocarcinoma. The study compared the use of the perioperative FLOT chemotherapy regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel) with the standard neoadjuvant (pre-surgery) chemoradiotherapy regimen (CROSS). Results presented at ASCO 2024 showed that perioperative FLOT led to significantly longer progression-free and overall survival outcomes, with fewer post-surgery complications as compared to CROSS. At the 2024 ASCO Direct™ Philadelphia conference, Dr Richard Kim highlighted that, based on findings from ESOPEC, FLOT might become the preferred regimen for fit patients with resectable esophageal cancer in the U.S.
Background
Esophageal adenocarcinoma is often treated with a combination of chemotherapy, radiation, and surgery, with the goal of shrinking patient’s tumors preoperatively and preventing recurrence of their cancer. Traditionally, the CROSS regimen—a combination of chemotherapy and radiation using carboplatin and paclitaxel, followed by surgery—has been widely used for these patients. The potential benefit of using perioperative FLOT, an approved chemotherapy regimen that has been proven effective in lower GI cancers (gastric cancer), led researchers to investigate whether the regimen could also provide superior survival outcomes for patients with upper GI cancer (esophageal adenocarcinoma).
Trial Design and Patients
ESOPEC was a phase III, multicenter, randomized study that enrolled patients with resectable esophageal adenocarcinoma. Of note, only patients with a clinical staging of T1N+ or T2 to T4A were included, while those with squamous cell carcinoma, or those with extensive disease (e.g., T4B) were excluded. Patients in the trial were assigned to one of two groups:
FLOT Group: Patients received four cycles of FLOT perioperatively (both before and after surgery).
CROSS Group: Patients received chemoradiotherapy with carboplatin and paclitaxel, followed by surgery, but without postoperative chemotherapy.
The primary endpoint in the trial was overall survival (OS), with secondary endpoints of progression-free survival (PFS), postoperative pathological response, and surgical complication rates.
Main Trial Results
Results presented at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO) showed a benefit of FLOT over CROSS in the following outcomes:
Progression-Free Survival (PFS): FLOT led to a median PFS of 38 months, nearly double that seen with CROSS, which was 19 months. This difference was statistically significant, indicating that FLOT was better than CROSS in delaying patient’s disease recurrence.
Overall Survival (OS): Median OS for patients in the FLOT group was 66 months, as compared to 37 months in the CROSS group. At five years, survival rates were approximately 50% with FLOT and 38% with CROSS.
Pathological Complete Response (pCR): Interestingly, despite the inclusion of radiation in the CROSS regimen, the FLOT group showed a higher rate of complete pathological responses (17% vs. 10%). This suggests that the chemotherapy alone in the FLOT regimen may provide sufficiently robust tumor eradication.
“We thought, at the time, the FLOT and CROSS regimens were pretty similar… But this is the first randomized study comparing these two regimens, and FLOT is the clear winner here… ”
Adverse Events and Toxicities
Notably, both treatment groups had similar rates of surgical complications and of postoperative mortality. There were no significant differences in safety observed in the study, and adverse events did not prevent completion of surgery or further treatment. Dr. Kim indicated that the FLOT treatment was well tolerated overall.
Conclusions and Faculty Insights
Dr Kim considered the findings from the ESOPEC as potentially practice-changing, especially for fit patients with resectable esophageal adenocarcinoma. He emphasized that FLOT, as a perioperative chemotherapy regimen, could offer superior long-term outcomes and disease control as compared with CROSS without increasing risk to patients. One potential caveat of the findings he noted was the absence of adjuvant nivolumab (Nivo) in the CROSS group (as this was not a standard treatment at the time the trial was designed), however, he emphasized that ongoing studies are comparing FLOT to CROSS in the context of added adjuvant (pot operative) nivolumab. Dr. Kim remarked that for eligible, healthy patients, perioperative FLOT might now be his preferred option, while CROSS plus Nivo might be an option for his less fit patients who cannot tolerate FLOT.
Speaker Disclosure information: Dr. Kim reported no relevant disclosures for this presentation.