FLOT Chemotherapy and CROSS Trimodality Regimen Result in Equivalent Survival for Patients With Gastroesophageal Junction Adenocarcinoma

A propensity-matched comparison found both the FLOT protocol and the CROSS trimodality regimen had equivalent survival for patients with locally advanced esophageal adenocarcinoma.

For this patient population, FLOT chemotherapy protocol (docetaxel, oxaliplatin, leucovorin, and 5-flourouracil) and the CROSS modality regimen (neoadjuvant chemoradiotherapy followed by surgical resection) are the current standard of treatment. Noel E Donlon, MD, Trinity St James’s Cancer Institute, Dublin, Ireland, and coauthors wrote, “In the absence of published Randomized Clinical Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics.”

This comparison included 222 patients with locally advanced esophageal adenocarcinoma who received either FLOT chemotherapy (n = 111) or the CROSS trimodality regimen (n = 111), from 2 high-volume centers. Sarcopenia and pulmonary function were evaluated pre-therapy and post-therapy. 

In the FLOT arm, 40% of patients tolerated the full prescribed regimen, compared with 92% in the CROSS regimen. The incidence of sarcopenia, as evaluated by computed tomography (CT), was 16% pretherapy in the FLOT arm and 33% posttherapy. In the CROSS arm, sarcopenia incidence was 14% pretherapy and 30% posttherapy (between arms, P < .01). In the FLOT arm, the median decrease in diffusion capacity for carbon monoxide was -8.25%, compared with -13.8% in the CROSS arm (between arms, P < .01). There was a major pathological response rate of 27% in the FLOT arm vs 44% in the CROSS arm (P = .03). While in-hospital mortality was 1% in the FLOT arm and 2% in the CROSS arm, there was an increased rate of respiratory failure in the CROSS arm (3% vs 13%, respectively; P < .001). The 3-year survival was 63% in the FLOT arm and 60% in the CROSS arm (P = .42).

“Both CROSS and FLOT resulted in equivalent survival,” Dr Donlon et al concluded, adding, “These data support clinical equipoise, caution, however, may be advised with CROSS in patients with greatest respiratory risk.”

Source: 

Donlon NE, Moran B, Kamilli A, et al. CROSS versus FLOT regimens in esophageal and esophagogastric junction adenocarcinoma. Ann Surg. 2022;276(5):792-798. doi: 10.1097.SLA.0000000000005617