ASCO 2024 Perioperative chemo outplays neoadjuvant CRT in esophageal cancer

medwireNews: The ESOPEC trial supports the use of perioperative chemotherapy over neoadjuvant chemoradiotherapy (CRT) in patients with resectable locally advanced esophageal adenocarcinoma. The perioperative FLOT regimen was associated with significantly better overall survival (OS) than the neoadjuvant CROSS regimen in the phase 3 study, investigator Jens Hoeppner, from the University of Bielefeld in Germany, reported at the 2024 ASCO Annual Meeting, held in Chicago, Illinois, USA. “Many patients in the US and Europe are still treated with the CROSS [CRT] protocol,” he commented in a press release. “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.” Outlining the rationale for the study, Hoeppner explained that both perioperative chemotherapy and neoadjuvant CRT, with surgery, are the current standards of care for resectable locally advanced esophageal adenocarcinoma, but it is not clear which multimodal approach is the most effective. The investigators therefore initiated the ESOPEC trial to conduct a head-to-head comparison of the strategies. A total of 438 patients with clinical stage T1N+M0 or T2–T4aN0/+M0 disease from 25 sites in Germany were randomly assigned to receive either: perioperative FLOT involving four cycles of preoperative FLOT (5-fluorouracil, leucovorin, oxaliplatin, docetaxel) in 8 weeks, followed by surgery and another four cycles of postoperative FLOT (n=221); or neoadjuvant CRT with the CROSS regimen involving 41.4 Gy of radiation plus five cycles of paclitaxel or carboplatin in 5 weeks, followed by surgery (n=217). The participants were followed up for a median of 55 months, at which point the primary endpoint of OS in the intention-to-treat population was a median of 66 months in the FLOT arm and 37 months in the CROSS arm, a significant difference equating to a hazard ratio (HR) of 0.70 in favor of FLOT. The 3-year OS rates were 57.4% and 50.7%, respectively. The findings were similar in the per-protocol population, with median OS durations in the FLOT and CROSS groups of 66 and 39 months, respectively, and a significant HR for death of 0.72. The OS rates at 3 years were a respective 58.1% and 52.6%. The FLOT approach also achieved significantly better progression-free survival (PFS) than the CROSS approach, with median durations in the intention-to-treat population of 38 versus 16 months, and an HR for progression or death of 0.66. Pathologic evaluation of the patients who underwent surgery (n=191 and 180 in the FLOT and CROSS groups, respectively) showed that the R0 resection rates were similar in the two arms, at 94.2% and 95.0%, respectively, while the rate of pathologic complete remission (defined as postoperative stage of ypT0 ypN0) was higher with FLOT, at 16.8% versus 10.0%. Hoeppner noted that “the postoperative morbidity was similar in the FLOT and CROSS groups” and the 30-day mortality rate was also comparable, at a respective 1.0% and 1.7%. Discussing the findings, he pointed out that “during the course of ESOPEC, new approaches have entered the treatment landscape for esophageal adenocarcinoma,” such as using adjuvant immunotherapy in case of noncomplete response after neoadjuvant CRT and surgery. But “despite promising initial studies, the impact of these approaches on overall survival is currently still unclear,” continued the presenter. Karyn Goodman (Icahn School of Medicine at Mount Sinai, New York, USA), who discussed the presentation, described the ESOPEC study as “practice changing,” and said that the improved survival with the perioperative FLOT versus neoadjuvant CROSS approach demonstrates “the superiority of a more intensive systemic therapy approach and early management of micrometastatic disease.” She expects that “FLOT will likely be adopted as a more standard approach in the United States for patients who are fit,” but for “patients who are not candidates for FLOT, CROSS is a reasonable option given equipoise from Neo-AEGIS.” Goodman highlighted, however, that the trial did not compare FLOT with CROSS followed by adjuvant nivolumab, which is recommended for patients who do not achieve a complete pathologic response based on the results of CheckMate 577, “so this is still a viable option.” She noted, however, that the OS data from the CheckMate trial are awaited. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group 2024 ASCO Annual Meeting; Chicago, Illinois, USA: 31 May–4 June

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ASCO 2024 Perioperative chemo outplays neoadjuvant CRT in esophageal cancer

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