Background: There is a lack of large-scale randomised data evaluating the impact of sex and age in patients undergoing chemotherapy followed by potentially curative surgery for oesophagogastric cancer. Patients and methods: Individual patient data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival analysis, hazard ratios (HRs) were calculated for patients aged <70 and 70 years, as well as between males and females. Mandard tumour regression grade (TRG) and, grade III toxicities were compared using logistic regression models to calculate odds ratios. All analyses were adjusted for the type of chemotherapy received. Results: 3265 patients were included for survival analysis (2668 [82%] male, 597 [18%] female; 2627 (80%) <70 years, 638 (20%) 70 years). A significant improvement in overall survival

Biliary tract cancers (BTC) comprise a group of rare and heterogeneous poor-prognosis tumours with the incidence of intrahepatic cholangiocarcinoma increasing over recent years. Combination chemotherapy with gemcitabine and cisplatin is the established first-line treatment for advanced BTC with a significant but modest survival advantage over monotherapy. There remains no accepted standard treatment in the second-line setting, although recent results from a randomised study have shown a survival benefit with 5-fluorouracil and oxaliplatin chemotherapy. Historically, clinical trials investigating targeted therapies in unselected BTC have failed to demonstrate significant clinical benefit. More recently, advancement in molecular exploration of BTC has shed light on the complex biological heterogeneity within these tumours and has also identified actionable genomic aberrations, such as fibroblast growth factor receptor 2 (FGFR2) gene fusions, isocitrate dehydrogenase (IDH) and BRAF mutations, which offer promise with the anticipation of increased responses and durable clinical benefit in selected patients. Several targeted drugs have now entered clinical development with some encouraging results being seen. Here we review the current and rapidly evolving therapeutic landscape of advanced BTC, including targeted therapies and immunotherapy. We also discuss how recent efforts and successes in BTC are overcoming the obstacles typically associated with precision medicine in rare cancers. Ultimately, the management of advanced BTC is likely to become molecularly selected in the near future with the hope of finally improving the bleak prognosis of patients with this disease.

201 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.

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