Perioperative Chemotherapy Prolongs OS in Esophageal Cancer

5-fluorouracil (FLOT protocol) in addition to perioperative chemotherapy with docetaxel, oxaliplatin, and leucovorin, led to a significant overall survival (OS) benefit vs neoadjuvant chemoradiation (CROSS protocol) in patients with resectable esophageal cancer, according to findings from the phase 3 ESOPEC trial (NCT02509286).¹

At a median follow-up of 55 months, patients who received the FLOT protocol (n = 221) achieved a median OS of 66 months compared with 37 months among those who were treated with the CROSS protocol (n = 217), according to findings presented at the 2024 ASCO Annual Meeting. The 3-year OS rates were 57% vs 51%, respectively. Moreover, among patients whose tumor regression status was known (n = 359), 35 patients in the FLOT arm experienced a pathological complete response vs 24 patients in the CROSS arm.

3D rendered medically accurate illustration of esophagus cancer: © Sebastian Kaulitzki - stock.adobe.com

“Many patients in the US and Europe are still treated with the CROSS radiochemotherapy protocol. Our study shows that patients with resectable esophageal cancer should have FLOT chemotherapy before and after the operation in order to optimize the chance of curing their tumors in the long term,” Jens Hoeppner , FAChirg, FACS, MD, the director of the Department of Surgery at University Medical Center, University of Bielefeld, in Detmold, Germany, stated in a press release.

ESOPEC was a prospective multicenter study that enrolled patients with esophageal adenocarcinoma across 25 sites in Germany. Eligible patients needed to be at least 18 years old, have received no prior abdominal or thoracic radiotherapy, have an ECOG performance status of 2 or less, and have adequate organ function. Patients were also required to have pretreatment stage cT1N+, M0 or cT2-4a, N0/+, M0 disease.³

Patients were randomly assigned 1:1 to receive either the FLOT or CROSS protocol. Those in the FLOT arm received repeated doses of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel every 2 weeks over 4 neoadjuvant cycles prior to surgery and 4 adjuvant cycles after surgery. In the CROSS arm, patients received neoadjuvant radiation therapy and concurrent chemotherapy with carboplatin and paclitaxel 5 weeks prior to surgery.

The primary end point was OS. Secondary end points included progression-free survival, recurrence-free survival, and postsurgical quality of life.

At baseline, the median age of all patients included in the study was 63 years. Most patients enrolled onto the trial were male (89%). Overall, 191 patients in the FLOT arm underwent surgery compared with 180 patients in the CROSS arm.¹

In the 90 days post-surgery, 3.2% of patients in the FLOT arm died compared with 5.6% in the CROSS arm. At the data cutoff, 97 and 121 patients died in these respective arms.

REFERENCES:

1. Chemotherapy before and after surgery may be new standard treatment for some patients with esophageal cancer. News Release. ASCO. June 2, 2024. Accessed June 2,2024.

2. Hoeppner J, Brunner T, Lordick F, et al. Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial).J Clin Oncol. 2024;42(suppl 17):LBA1.

3. Perioperative chemotherapy compared to neoadjuvant chemoradiation in patients with adenocarcinoma of the esophagus (ESOPEC). ClinicalTrials.gov. Updated May 8, 2024. Accessed June 1, 2024. https://clinicaltrials.gov/study/NCT02509286