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Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR\/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet\u2010ring cell component (A:47% B:43%). No between\u2010arm difference in pCR\/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0\u2010resection rate compared with FLOT alone (A:82% B:96%; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.009). In addition, the median disease\u2010free survival was numerically improved in Arm B (A:21\u2009months B:32\u2009months, HR 0.75, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.218), while the median overall survival was similar in both treatment arms (A:45\u2009months B:46\u2009months, HR 0.94, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first\u2010third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non\u2010surgical grade\u2009\u2265\u20093 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted.<\/jats:p>","DOI":"10.1002\/ijc.34495","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T09:24:13Z","timestamp":1678267453000},"page":"153-163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II\/III trial of the German AIO and Italian GOIM"],"prefix":"10.1002","volume":"153","author":[{"given":"Thorsten O.","family":"Goetze","sequence":"first","affiliation":[{"name":"Institute for Clinical Cancer Research IKF  Frankfurt Germany"},{"name":"Krankenhaus Nordwest, UCT\u2010University Cancer Center  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf\u2010Dieter","family":"Hofheinz","sequence":"additional","affiliation":[{"name":"Mannheim Cancer Center University Hospital Mannheim  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Gaiser","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Medical Faculty Mannheim University of Heidelberg  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Schmalenberg","sequence":"additional","affiliation":[{"name":"IV. 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