Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real‐world cohort

In 2019, the FLOT4 protocol was established as the new standard for perioperative therapy in patients with locally advanced gastroesophageal and gastric cancer. Whether this protocol is beneficial in a real‐world setting remains a question with limited answers to date. In our study, a large cohort of unselected patients treated with FLOT4 was analyzed and compared to protocols based on 5‐FU/platinum derivative. This retrospective analysis included patients with locally advanced gastroesophageal and gastric cancer treated with perioperative FLOT or 5‐FU/platinum derivative at University Hospital, Bonn between 2010 and 2022 in a curative setting (n = 99). Overall survival, disease‐free survival, therapy response and therapy complications were analyzed. Patients treated with FLOT showed a statistically significant longer median overall survival of 57.8 vs 28.9 months (HR: 0.554, 95% CI: 0.317‐0.969, P = .036). Moreover, pathological tumor regression (pTR) was significantly higher in the FLOT group compared to the 5‐FU/platinum group (P = .001). Subgroup analysis showed a favorable survival benefit for the FLOT vs 5‐FU/platinum derivate in patients with AEG and non‐signet cell carcinoma. Overall, FLOT was tolerated well but CTCAE ≥3 grade neutropenia and diarrhea occurred more often within the FLOT group. Similar to the prospective phase II/III trials, FLOT4 was the best protocol for patients with locally advanced gastroesophageal and gastric cancer as perioperative therapy in terms of overall survival and pathological response rate compared to 5‐FU/platinum derivative protocols. Interestingly, patients with gastroesophageal cancer benefitted more from this therapy. In contrast, patients with signet ring cells appear not to benefit from addition of docetaxel.