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Background: ICONIC is a single-arm phase II trial investigating the safety and efficacy of perioperative FLOT-A in resectable OGA. Following a 3+3 design safety run-in phase, standard dose FLOT with 10mg/kg IV avelumab (dose level 0) q2weeks was taken forward into the main study. The aims of this pre-planned interim analysis were to assess perioperative safety and R0 resection rates. Methods: The interim analysis occurred once the 15th patient treated at dose level 0 reached 30 days post-surgery. Results: At data cut-off, 15 patients had received at least one cycle of FLOT-A and had undergone resection. The median age of patients was 63y (range: 25 – 73). 71% had an ECOG PS of 0. 60% of tumours were staged as T3 at baseline and 40% T2; 67% were N0, 7% N1 and 27% N2. Due to 5-FU related cardiac toxicity, two patients switched to alternative chemotherapy without 5-FU and avelumab. 13/15 patients (87%) completed 4 cycles of pre-operative FLOT-A; of these, five patients had avelumab omitted for one cycle for toxicity evaluation and management. 9/15 patients (60%) experienced a G3/4 adverse event (AE). These were FLOT-A-related in 8/15 patients (53.3%). The commonest G3/4 AEs were febrile neutropenia, neutropenia and diarrhoea. Median time from last chemotherapy to surgery was 6.4 weeks. No delays or failure to proceed to surgery occurred due to avelumab-related complications. 7% of patients had an American Society of Anaesthesiologists (ASA) preoperative risk score of I, 47% a score of II and 47% a score of III. 73% of patients had operations involving a thoracic approach (10 minimally invasive Ivor-Lewis oesophagogastrectomy with two field radical lymphadenectomy, 1 left thoracoabdominal oesophagogastrectomy and 4 gastrectomy with D2 lymphadenectomy). Median time to extubation was 6h (IQR: 4-24). The median Acute Physiology and Chronic Health Evaluation (APACHE) score at day 1 post-op was 12 (IQR: 10-15) with a median of 3 days (IQR: 2-4) of CCU care. No unexpected complications were reported intra-operatively or during post-operative recovery in FLOT-A treated patients. 5/14 evaluable patients at data cut-off (35.7%) had Clavien-Dindo grade II post-operative complications and 3/14 (21.4%) grade IIIa complications; of these 1 patient had an anastomotic leak that was treated endoscopically. There were no emergency re-operations. All 15 patients achieved R0 resections and were discharged home after a median of 13d (IQR: 11-16) in hospital. Conclusions: To date, FLOT-A has not led to unexpected or unusually severe perioperative complications in the context of major complex upper GI surgery for resectable OGA. Clinical trial information: NCT03399071.