FLOT chemotherapy beat preoperative chemoradiotherapy in patients with locally advanced adenocarcinoma.
Patients with resectable oesophageal adenocarcinoma have longer survival and progression-free survival if treated with perioperative chemotherapy compared to preoperative chemoradiotherapy, according to new research.
But the study of more than 400 adults across 25 German centres, published in the NEJM, found that perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) also came with more adverse events.
“The current trial showed that overall survival was better with FLOT than with preoperative chemoradiotherapy among patients with resectable oesophageal adenocarcinoma, including those with a clinical lymph-node stage of cN+ and those with a clinical tumour stage of cT3 or cT4, who made up most of the trial population,” author and surgeon Professor Jens Hoeppner and colleagues wrote.
“Whether de-escalation to a chemotherapy doublet or a switch to preoperative chemoradiotherapy is the preferred approach in patients to whom FLOT cannot be given because of coexisting conditions or in those with FLOT-related adverse events remains a question that our trial cannot answer.”
Patients in the phase 3, unblinded controlled trial were randomly assigned to receive either perioperative chemotherapy with FLOT plus surgery or preoperative chemoradiotherapy plus surgery.
Patients in the FLOT group had four cycles of chemotherapy before surgery and then another four cycles after surgery. The chemoradiation therapy was based on the CROSS regimen, which included 41.4Gy radiotherapy and carboplatin plus paclitaxel chemotherapy.
The primary endpoint was survival, and 57.4% of the FLOT group survived at three years compared to 50.7% in the chemoradiotherapy group. Overall survival rates were 66 months and 37 months, respectively.
Similarly, progression-free survival in the FLOT group was 51.6% compared to 35.0% in the chemoradiotherapy group at three years.
At five years, overall survival was 50.6% in the FLOT group compared to 38.7% in the chemoradiotherapy group.
Related
But grade 3 or higher adverse events occurred in 58% of the FLOT group compared to 50% of the chemoradiotherapy group. Serious adverse events occurred in 47.3% of the FLOT group compared to 41.8% of the chemoradiotherapy group.
“Hoeppner and colleagues are to be congratulated for their trial. In patients with oesophageal adenocarcinoma and no serious coexisting conditions that limit the use of FLOT, perioperative chemotherapy rather than chemoradiotherapy is an appropriate first choice,” Dr David Kelsen, a US gastrointestinal medical oncologist, wrote in an accompanying editorial.
Chemoradiotherapy still had a role in treating patients for whom FLOT harms outweighed the benefits, he wrote.
“The use of perioperative systemic therapies with even greater effectiveness, including agents tailored to the tumour profile, is likely to further improve survival among patients with oesophageal adenocarcinoma.”
“Preoperative chemoradiotherapy is currently listed as the preferred approach in the National Comprehensive Cancer Network guidelines. With the development of more-effective systemic chemotherapy regimens, the use of radiotherapy (which has its own toxic effects) has been questioned,” he wrote.
“Locoregional recurrence only (a reason for including radiotherapy with carboplatin and paclitaxel chemotherapy), although occurring in more patients in the FLOT group, was uncommon (in 17 vs. 9 patients); distant recurrence occurred in a substantially higher number of patients in the preoperative-chemoradiotherapy group. The percentage of patients with R0 resection was nearly identical in the trial groups (approximately 95%).”
