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BackgroundThere is increasing evidence for the use of exercise in cancer patients and data supporting enhanced tumour volume reduction following chemotherapy in animal models. To date, there is no reported histopathological evidence of a similar oncological benefit in oesophageal cancer.MethodsA prospective non-randomised trial compared a structured prehabilitation exercise intervention during neoadjuvant chemotherapy and surgery versus conventional best-practice for oesophageal cancer patients. Biochemical and body composition analyses were performed at multiple time points. Outcome measures included radiological and pathological markers of disease regression. Logistic regression calculated ORs with 95% CI for the likelihood of pathological response adjusting for chemotherapy regimen and chemotherapy delivery.ResultsComparison of the Intervention (n=21) and Control (n=19) groups indicated the Intervention group had higher rates of tumour regression (Mandard TRG 1–3 Intervention n=15/20 (75%) vs Control n=7/19 (36.8%) p=0.025) including adjusted analyses (OR 6.57; 95% CI 1.52 to 28.30). Combined tumour and node downstaging (Intervention n=9 (42.9%) vs Control n=3 (15.8%) p=0.089) and Fat Free Mass index were also improved (Intervention 17.8 vs 18.7 kg/m2; Control 16.3 vs 14.7 kg/m2, p=0.026). Differences in markers of immunity (CD-3 and CD-8) and inflammation (IL-6, VEGF, INF-y, TNFa, MCP-1 and EGF) were observed.ConclusionThe results suggest improved tumour regression and downstaging in the exercise intervention group and should prompt larger studies on this topic.Trial registration numberNCT03626610.

Simple Summary High grade neuroendocrine tumours and carcinomas (NETs/NECs) behave aggressively and have limited survival outcomes. The mainstay of therapy is systemic therapy, in which the associated side-effects are a key consideration in a palliative population. We have conducted a retrospective review of patients with high grade NETs and NECs to determine possible tests that will predict survival before patients start treatment. This will allow patients to avoid potentially toxic treatment that is unlikely to be of benefit. Abstract Background: High-grade neuroendocrine tumours and carcinomas (NET/NECs) behave aggressively, typically presenting at an advanced stage. Prognosis is poor, with median survival between 5 and 34 months. The mainstay of treatment is palliative systemic therapy. However, therapy carries a risk of toxicity, which can reduce quality of life. Therefore, accurate prognostic scores for risk stratification of patients with high-grade NET/NECs are needed to help guide patient management to decide whether active treatment is likely to improve overall survival (OS). We aimed to compare the prognostic ability of published prognostic scores to predict OS in a cohort of patients with high-grade NET/NECs of any primary site. Methods: Treatment, biochemical and clinicopathological data were collected retrospectively from 77 patients with high-grade NET/NECs across three hospitals between 2016 and 2020. Variables including performance status (PS), Ki-67, age at diagnosis, previous treatment and presence of liver metastases were recorded. Pre-treatment neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, modified Glasgow prognostic score (mGPS), and gastrointestinal neuroendocrine carcinoma (GI-NEC) score were derived. Univariable and multivariable survival analyses were used to assess prognostic ability. Results: The median age of the cohort was 63 years (range: 31–85); 53% of subjects were female. Grade 3 NETs (G3-NETs) were identified in 32 patients and NECs in 45 patients. The median OS was 13.45 months (range: 0.87–65.37) with no difference observed between G3-NETs and NECs. Univariable analysis revealed that NLR (n = 72, p = 0.049), mGPS (n = 56, p = 0.003), GI-NEC score (n = 27, p = 0.0007) and Ki-67 (n = 66, p = 0.007) were significantly associated with OS. Multivariable analysis confirmed that elevated mGPS (p = 0.046), GI-NEC score (p = 0.036), and Ki-67 (p = 0.02) were independently prognostic for reduced OS across the entire cohort. mGPS was identified as an independent prognostic factor in G3-NETs. Independent predictors of OS in NECs were PS and Ki-67. Conclusions: mGPS, PS and Ki-67 are independent prognostic markers in high-grade NET/NEC patients. Our study supports the use of these prognostic scores for risk stratification of patients with high grade cancers and as useful tools to guide treatment decisions.

Background: GO2 sought to optimise chemotherapy dosing in older/frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. Methods: Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable. Two randomisation options were available: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (doses as used in the standard epirubicin/oxaliplatin/capecitabine regimen), B (0·8x A) or C (0·6x A). Non-inferiority of PFS was assessed using boundary HR=1·34, selected by a forum of patients and clinicians. Overall Treatment Utility (OTU), which combines efficacy, toxicity, QL and patient value/acceptability, was scored at nine weeks. Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, they could enter the CHEMO-BSC randomisation, comparing Level C versus best supportive care. Findings: 514 patients entered the CHEMO-INTENSITY randomisation: non-inferior PFS was confirmed for B vs A (HR=1·09 [CI=0·89-1·32]) and C vs A (HR=1·10 [0·90-1·33]). Level C produced less toxicity and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in the younger, fitter patients. 45 patients entered the CHEMO-BSC randomisation: overall survival was non-significantly longer with chemotherapy: median 6·1 vs 3·0 months, HR=0·69 [0·32-1·48], p=0·34. In multivariate analysis, baseline frailty, QL and neutrophil:lymphocyte ratio were independently associated with OTU, so can be combined in a model to estimate the probability of better or worse outcome. Interpretation: Reduced-intensity chemotherapy provided non-inferior efficacy with an improved patient experience. Baseline geriatric assessment can help predict the utility of chemotherapy. Trial Registration: [Trial registration: ISRCTN44687907] Funding Statement: Cancer Research UK [CRUK/12/022] Declaration of Interests: Dr. Grabsch reports personal fees from Merck Sharpe Dome, outside the submitted work; all other authors have nothing to declare. Ethics Approval Statement: This study was approved by the UK National Research Ethics Service and overseen by independent Trial Steering and Data Monitoring & Ethics Committees (TSC; IDMC).

Background: Advanced biliary tract cancer (ABC) has a poor prognosis for which cisplatin-gemcitabine is the reference first-line chemotherapy. No robust evidence is available for second-line chemotherapy. Methods: Patients with ABC who progressed on first-line cisplatin-gemcitabine were randomised to active symptom control (ASC) and oxaliplatin and 5-fluorouracil (FOLFOX) or ASC alone. The primary end-point was overall survival (OS); recruitment of 162 patients was required, to deliver 148 events (hypothesised hazard ratio (HR) 0.63; 80% power; 5% two-sided alpha). Secondary end-points included progression-free survival (PFS) and response rate (ASC+FOLFOX arm only). Results: A total of 162 patients were randomised (81 in each arm) between 27-Mar-2014 and 04-Jan-2018). The median age was 65 years (range 26-84); 80 (49%) were male and the primary tumour sites were intrahepatic cholangiocarcinoma (CCA) 72 (44%), extrahepatic CCA 45 (28%), gallbladder 34 (21%) and ampullary cancer 11 (7%). After 150 OS events, the adjusted HR was 0.69 (95%CI-0.50-0.97; p=0.031; ASC+FOLFOX vs ASC). Median OS (months (m)), 6m and 12m OS-rate (%) were 6.2m, 50.6% and 25.9% for the ASC+FOLFOX and 5.3m, 35.5%, 11.4% for the ASC arm, respectively. The median PFS was 4.0 months (95%-CI 3.2-5.0); the response rate was 5% and the disease control rate 33%. Grade 3-5 adverse events were reported in 56 (69%) and 42 (52%) patients in the ASC+FOLFOX and ASC arm, respectively, including two chemotherapy-related deaths. Conclusion: FOLFOX improved OS after progression to cisplatin-gemcitabine with a clinically-meaningful increase in 6m and 12m OS rate. FOLFOX should become standard-of-care in second-line for ABC. Trial Registration: NCT01926236, EudraCT: 2013-001812-30. Funding Statement: The study was sponsored by The Christie NHS Foundation Trust. The ABC-6 study was funded by Cancer Research UK (CRUK/13/004), StandUpToCancer, AMMF (The UK Cholangiocarcinoma Charity) and The Christie Charity. The Cholangiocarcinoma Foundation provided funding translational research. Dr Angela Lamarca received funding from ESMO (European Society for Medical Oncology), SEOM (Sociedad Espanola de Oncologia Medica) and Conquer Cancer Foundation (Young Investigator Award) fellowship programs and from The Christie Charity. Declaration of Interests: Dr Angela Lamarca received travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan and Delcath; speaker honoraria from Merck, Pfizer, Ipsen and Incyte; advisory honoraria from EISAI, Nutricia Ipsen, QED and Roche; she is also a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. Prof Daniel H Palmer declares research grants from AstraZeneca, Bayer, BMS, Nucana, Sirtex; and Consulting or Advisory roles for AstraZeneca, Bayer, BMS, Eisai, MSD, Servier, Roche. Harpreet Singh Wasan declares no conflict of interest associated to this work. Dr Paul J Ross declares research grants from research grants from Sanofi, Bayer; Consulting or Advisory roles for Bayer, BMS, Eisai, Sirtex, Roche; speaker fees from Amgen, Roche, Servier; Travel grants from Bayer, Roche, Servier. Dr Yuk Ting Ma declares speaker honoraria and advisory roles for Bayer, Eisai and Roche. Dr Arvind Arora declares no conflict of interest. Dr Stephen Flak declares no conflict of interest. Dr Roopinder Gilmore declares no conflict of interest. Prof Jon Wadsley declares research grants from AstraZeneca and Sanofi-Genzyme and Consulting or Advisory roles for Lilly, AstraZeneca, Sanofi Genyme, Eisai, AAA, Roche, Novartis, Ipsen. Dr Kinnari Patel declares no conflict of interest. Alan Anthony declares no conflict of interest. Prof Anthony Maraveyas declares research grants from Pfizer, BMS and Bayer. Speaker fees from BMS. Bayer Ipsen, EUSA Pharma, Daiichi Sankyo and Pfizer and advisory roles for Bayer ,BMS, Leo, Pfizer, Merck and Ipsen. Dr Tim Iveson declares no conflict of interest. Dr Justin S Walters received educational support for travel and conference attendance from Mylan and Ipsen, and speaker honoraria from Mylan. Dr Claire Hobbs declares no conflict of interest. Safia Barber declares no conflict of interest. David Ryder declares no conflict of interest. Prof John Ramage declares research grants, speaker fees and advisory roles for Ipsen, Novartis and AAA. Linda M Davies declares no conflict of interest. Prof John Bridgewater declares Consulting or Advisory role for Merck Serono, SERVIER, Roche, Bayer, AstraZeneca, Incyte and Basilea; travel support from MSD oncology, Merck Serono, Servier and BMS. Prof Juan W Valle declares Consulting or Advisory role for Agios, AstraZeneca, Delcath Systems, Keocyt, Genoscience Pharma, Incyte, Ipsen, Merck, Mundipharma EDO, Novartis, PCI Biotech, Pfizer, PierisPharmaceuticals, QED and Wren Laboratories; Speakers’ Bureau for Imaging Equipment Limited Ipsen Novartis Nucana; and Travel Grants from Celgene and Nucana. Ethics Approval Statement: The study was conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. The study protocol was approved by a research ethics committee and all patients were required to provide written informed consent.

PURPOSE In the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274 ), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy. PATIENTS AND METHODS A total of 553 patients were enrolled in the trial. Of 203 patients with a germline BRCA mutation (g BRCAmut), 99 had a PR and 104 had a CR to their last platinum-based therapy; of 350 patients without a confirmed g BRCAmut (non–g BRCAmut), 173 had a PR and 177 had a CR. Post hoc analyses were carried out to evaluate safety and the risk of progression in these patients according to g BRCAmut status and response to their last platinum-based therapy. Ovarian cancer–specific symptoms and quality of life were assessed using the Functional Assessment of Cancer Therapy–Ovarian Symptom Index. RESULTS Progression-free survival was improved in patients treated with niraparib compared with placebo in both the g BRCAmut cohort (PR: hazard ratio [HR], 0.24; 95% CI, 0.131 to 0.441; P < .0001; CR: HR, 0.30; 95% CI, 0.160 to 0.546; P < .0001) and the non–g BRCAmut cohort (PR: HR, 0.35; 95% CI, 0.230 to 0.532; P < .0001; CR: HR, 0.58; 95% CI, 0.383 to 0.868; P = .0082). The incidence of any-grade and grade 3 or greater adverse events was manageable. No meaningful differences were observed between niraparib and placebo in PR and CR subgroups with respect to patient-reported outcomes. CONCLUSION Patients achieved clinical benefit from maintenance treatment with niraparib regardless of response to the last platinum-based therapy.

Background: Pancreatic neuro-endocrine tumours (pNETs) are rare tumours, constituting less than 5% of pancreatic tumours. Of these cases, only an estimated 6% present with functional secretion of more than one hormone. Clinical Case: A 72-year-old woman was admitted to the acute frailty ward with symptoms of generalized weakness, fatigue and reduced exercise tolerance with shortness of breath on exertion. She reported unintentional weight loss of 16 kg in the preceding 3 months and widespread migratory rash with epidermal breakdown in the lower legs that was resistant to antibiotic therapy. Initial investigations on admission revealed severe anaemia with a haemoglobin (Hb) of 51 g/L that was refractory to blood transfusion, prompting gastroscopy that showed erosive gastritis. CT/MRI scans revealed a 24 mm solid arterial-enhancing mass lesion in the uncinate process of the pancreas, highly suggestive of a neuroendocrine tumour (NET). Histopathological examination of a skin biopsy showed intraepithelial vacuolisation of the cells in the upper epidermis, neutrophilic infiltration with psoriasiform hyperplasia and confluent parakeratosis; typical features of necrolytic migratory erythema (NME). Fasting serum gut hormone profile prior to omeprazole therapy was consistent with multiple functioning NET with elevated serum glucagon level (>500 pmol/L) and hypergastrinaemia (274 pmol/L). Fasting serum glucose level was 4.5 mmol/L and serum albumin was 24 g/L. Elevated serum fasting serum glucagon and gastrin levels strongly supported diagnosis of neuroendocrine tumour resulting in normoglycaemic glucagonoma syndrome (NME, weight loss without diabetes mellitus) and Zollinger-Ellison syndrome (anaemia and hyperchlorhydria). The rash resolved rapidly less than a week after commencing medical management with octreotide, a somatostatin receptor analogue. She was also commenced on high dose PPI therapy. Somatostatin receptor scintigraphy was performed that confirmed a somatostatin-avid primary tumour in the pancreas without distant metastases. Surveillance will include blood glucose monitoring, interval rescanning with CT abdomen and pelvis with contrast and octreotide scan to assess for metastases. Surgical resection of the tumour will be considered as the patient's performance status improves. Conclusion: We report a rare case of a patient diagnosed with a multiple functioning pNET. The clinician must always consider unconventional rashes as dermatological manifestations of systemic disease. A normal fasting serum glucose level is not a reliable exclusion criterion of glucagonoma syndrome due to functioning insulin secretion from beta pancreatic islet cells. Isolated measurement of fasting serum gastrin level is not appropriate for diagnosis of Zollinger-Ellison syndrome in patients treated with proton pump inhibitors or histamine receptor antagonists. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Proximal oesophageal stent deployment continues to provide challenges due to the proximity of the upper oesophageal sphincter and the associated subsequent complications such as globus sensation and stent migration. Patients with cervical oesophageal cancer have previously had limited stenting options available to them with a paucity of the literature describing the radiological technique for successfully placing these high-risk stents. In this paper, we present our experience using the Taewoong Niti-S CERVICAL Oesophageal Stent. We describe our method for stent deployment highlighting the importance of pre-procedural planning in ensuring an adequate proximal landing zone for the short proximal flare of the stent. Furthermore, we outline how we have adapted our placement technique to incorporate a routine pre-dilatation stage which has optimised retrieval of the proximal to distal deployment system. We have placed eight cervical oesophageal stents within our institution. Contrast swallows in all the patients following stent deployment have demonstrated free flow of contrast to the stomach with all patients reporting symptomatic relief and no foreign body/globus sensation. There has been one episode of stent migration but no incidence of oesophageal perforation or haemorrhage. Evolution of stenting technique and the properties of the stents themselves are improving accuracy of stent placement in relation to the important landmark of the upper oesophageal sphincter. Stenting of cervical oesophageal malignancy has proved successful in our institution and provided symptom relief for a subset of palliative patients who were previously unable to benefit from oesophageal stenting.

Each of the three patients reported in this article presented with dermatomyositis at various stages of their advanced ovarian cancer. Dermatomyositis was the presenting feature and preceded the diagnosis of ovarian cancer by several months in one patient. In another patient, dermatomyositis occurred just prior to the scheduled third cycle of palliative chemotherapy after surgical debulking for stage 4 disease. The third patient presented with pathognomonic diagnostic features of dermatomyositis after ovarian cancer recurrence. Diagnosis was delayed in at least two of these patients; however, once appropriately diagnosed, each patient responded well to immunomodulatory treatment. In one patient, initiation of oral prednisolone seemed to correlate with a steady improvement in her proximal myopathy. A pulsed methylprednisolone approach was used in another patient with conversion to a tapering dose of oral prednisolone to good effect. In the patient in whom the most severe myopathy affecting bulbar muscle groups was demonstrated, an infusion of 5 days of intravenous immunoglobulin produced an eventual improvement in her steroid-refractory myopathy.

Summary Background EGFR overexpression occurs in 27–55% of oesophagogastric adenocarcinomas, and correlates with poor prognosis. We aimed to assess addition of the anti-EGFR antibody panitumumab to epirubicin, oxaliplatin, and capecitabine (EOC) in patients with advanced oesophagogastric adenocarcinoma. Methods In this randomised, open-label phase 3 trial (REAL3), we enrolled patients with untreated, metastatic, or locally advanced oesophagogastric adenocarcinoma at 63 centres (tertiary referral centres, teaching hospitals, and district general hospitals) in the UK. Eligible patients were randomly allocated (1:1) to receive up to eight 21-day cycles of open-label EOC (epirubicin 50 mg/m 2 and oxaliplatin 130 mg/m 2 on day 1 and capecitabine 1250 mg/m 2 per day on days 1–21) or modified-dose EOC plus panitumumab (mEOC+P; epirubicin 50 mg/m 2 and oxaliplatin 100 mg/m 2 on day 1, capecitabine 1000 mg/m 2 per day on days 1–21, and panitumumab 9 mg/kg on day 1). Randomisation was blocked and stratified for centre region, extent of disease, and performance status. The primary endpoint was overall survival in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. After a preplanned independent data monitoring committee review in October, 2011, trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. This study is registered with ClinicalTrials.gov, number NCT00824785. Findings Between June 2, 2008, and Oct 17, 2011, we enrolled 553 eligible patients. Median overall survival in 275 patients allocated EOC was 11·3 months (95% CI 9·6–13·0) compared with 8·8 months (7·7–9·8) in 278 patients allocated mEOC+P (hazard ratio [HR] 1·37, 95% CI 1·07–1·76; p=0·013). mEOC+P was associated with increased incidence of grade 3–4 diarrhoea (48 [17%] of 276 patients allocated mEOC+P vs 29 [11%] of 266 patients allocated EOC), rash (29 [11%] vs two [1%]), mucositis (14 [5%] vs none), and hypomagnesaemia (13 [5%] vs none) but reduced incidence of haematological toxicity (grade ≥3 neutropenia 35 [13%] vs 74 [28%]). Interpretation Addition of panitumumab to EOC chemotherapy does not increase overall survival and cannot be recommended for use in an unselected population with advanced oesophagogastric adenocarcinoma. Funding Amgen, UK National Institute for Health Research Biomedical Research Centre.

Annualised figures show an up to 7-fold higher incidence of vascular thromboembolism (VTE) in patients with advanced pancreatic cancer (APC) compared to other common malignancies. Concurrent VTE has been shown to confer a worse overall prognosis in APC.One hundred and twenty three APC patients were randomised to receive either gemcitabine 1000 mg/m(2) or the same with weight-adjusted dalteparin (WAD) for 12 weeks. Primary end-point was the reduction of all-type VTE during the study period. NCT00462852, ISRCTN: 76464767.The incidence of all-type VTE during the WAD treatment period (100 days from randomisation) was reduced from 23% to 3.4% (p = 0.002), with a risk ratio (RR)of 0.145, 95% confidence interval (CI) (0.035-0.612) and an 85% risk reduction. All-type VTE throughout the whole follow-up period was reduced from 28% to 12% (p = 0.039), RR = 0.419, 95% CI (0.187-0.935) and a 58% risk reduction. Lethal VTE100 days was seen only in the control arm, 8.3% compared to 0% (p = 0.057), RR = 0.092, 95% CI (0.005-1.635).Weight adjusted dalteparin used as primary prophylaxis for 12 weeks is safe and produces a highly significant reduction of all-type VTE during the prophylaxis period. The benefit is maintained after dalteparin withdrawal although decreases with time.

To evaluate the combination of the gastrin antagonist Z-360 and gemcitabine for advanced pancreatic cancer.Previously untreated patients with PC were randomly allocated to Z-360 120 mg, 240 mg or placebo. Z-360/placebo was given on day -3 and gemcitabine 1000 mg/m(2) commenced on day 1 followed by Z-360 on day 2. Thereafter Z-360/placebo was given twice daily concurrently with standard dose of gemcitabine. Pharmacokinetics for both drugs was measured alone and in combination. Toxicity, response and quality of life were also recorded.Thirty-three patients with a median age of 62 years were randomised of which six had locally advanced disease and 26 had metastatic disease. Analysis of the area under the plasma concentration versus time curve (AUC), the maximum observed concentration (Cmax(obs)) and the time of the maximum observed concentration (Tmax(obs)) for Z-360, gemcitabine and 2,2-difluorodeoxyuridine (dFdU), could not exclude an effect on the systemic exposure to Z-360, gemcitabine and dFdU when co-administration of Z-360 and gemcitabine was compared with single agent administration. The most commonly reported adverse events were nausea, abdominal pain, vomiting and fatigue. At the end of the study, 62.5%, 25% and 60% had stable disease in the 120 mg, 240 mg and placebo group, respectively. A higher proportion of patients in Z-360 groups reported improvement in pain.Z-360 is safe and well tolerated when combined with gemcitabine. A Phase III trial is needed to determine whether the combination of Z-360 and gemcitabine is superior to gemcitabine alone in advanced PC.

5517 Background: Therapeutic paradigms for recurrent OC vary by geography. Maintenance following response to platinum-based chemotherapy (Plat) is standard in Europe, whereas in the US maintenance is considered following complete response (CR) vs treatment for partial response (PR). Niraparib is a highly selective PARP 1/2 inhibitor (PARPi). In preclinical studies it concentrates in the tumor relative to plasma, delivering > 90% durable PARP inhibition and antitumor effects. Niraparib demonstrated significantly longer PFS vs placebo (P) in pts with recurrent OC following a CR or PR to Plat in the randomized, controlled, double-blind phase 3 ENGOT-OV16/NOVA trial. Methods: Pts with recurrent OC, no prior PARPi use, ≥2 prior courses of Plat, and response to most recent Plat were eligible. Pts were assigned to 1 of 2 cohorts on the basis of g BRCA testing (g BRCAmut or non-g BRCAmut) and randomized 2:1 within each cohort to niraparib 300 mg or P qd until progressive disease (PD). Randomization occurred up to 8 weeks after last dose of the most recent Plat. Pts were stratified by time to progression after penultimate Plat (6 to < 12 months or ≥12 months), prior use of bevacizumab (yes/no), and response to most recent Plat (CR or PR). PFS was measured from time of randomization to death or earliest PD as assessed by independent review committee. Results: 49% of pts (niraparib: 67/138; P: 32/65) in the g BRCAmut and ~49% of pts (niraparib: 117/234 [50%]; P: 56/116 [48%]) in the non-g BRCAmut cohorts entered NOVA with a PR following their most recent Plat. At time of unblinding, 30 (45%) niraparib and 23 (72%) P pts in the g BRCAmut and 65 (56%) niraparib and 45 (80%) P pts in the non-g BRCAmut cohorts had PFS events. PFS hazard ratios (95% CI) were 0.24 (0.131–0.441) in g BRCAmut and 0.35 (0.230–0.532) in non-g BRCAmut cohorts for pts who had a PR to their most recent platinum regimen. This compared favorably to the overall NOVA study results, where PFS hazard ratios (95% CI) were 0.27 (0.173–0.410) in g BRCAmut and 0.45 (0.338–0.607) in non-g BRCAmut cohorts. Conclusions: Niraparib treatment provided significant benefit to pts with recurrent OC who achieved a PR following Plat. Clinical trial information: NCT01847274.

Background REAL3 (Randomised ECF for Advanced or Locally advanced oesophagogastric cancer 3) was a phase II/III trial designed to evaluate the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in untreated advanced oesophagogastric adenocarcinoma, or undifferentiated carcinoma. MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) was a phase III study which demonstrated that peri-operative epirubicin, cisplatin and infused 5-fluourouracil (ECF) improved survival in early oesophagogastric adenocarcinoma. Patients and methods Analysis of response rate (RR; the primary end-point of phase II) and biomarkers in the first 200 patients randomised to EOC or modified dose (m) EOC+P in REAL3 was pre-planned to determine if molecular selection for the on-going study was indicated. KRAS, BRAF and PIK3CA mutations and PTEN expression were assessed in pre-treatment biopsies and results correlated with response to mEOC+P. Association between these biomarkers and overall survival (OS) was assessed in MAGIC patients to determine any prognostic effect. Results RR was 52% to mEOC+P, 48% to EOC. Results from 175 assessable biopsies: mutations in KRAS (5.7%), BRAF (0%) , PIK3CA (2.5%) and loss of PTEN expression (15.0%). None of the biomarkers evaluated predicted resistance to mEOC+P. In MAGIC, mutations in KRAS , BRAF and PIK3CA and loss of PTEN ( phosphatase and tensin homolog ) were found in 6.3%, 1.0% , 5.0% and 10.9%, respectively, and were not associated with survival. Conclusions The RR of 52% in REAL3 with mEOC+P met pre-defined criteria to continue accrual to phase III. The frequency of the mutations was too low to exclude any prognostic or predictive effect.

Most patients with cancers of the stomach, oesophagus or gastroesophageal junction ultimately develop metastatic or inoperable disease, rendering them incurable. They can, however, benefit from a variety of palliative interventions inving the multidisciplinary team, including chemotherapy, radiotherapy, endoluminal stenting, laser, or surgery. Often a combination of such strategies will be used to control symptoms, and maintain or improve quality of life. In this article, we review these multidisciplinary interventional approaches in patients with gastroesophageal cancers, and highlight future trends.

4092 Background: Perioperative chemotherapy is a standard treatment for localised gastric/OGJ adenocarcinoma. B is a monoclonal antibody targeting vascular endothelial growth factor A. Addition of ...

4131 Background: EOC is a standard treatment option for advanced OG cancer. Epidermal growth factor receptor (EGFR) overexpression is common in OG cancer and associated with poor prognosis. P is a ...

Background Effective first-line treatment for patients with advanced biliary tract cancer (BTC) has been established with a median survival of approaching 12 months (NEJM 2010; 362:1273). No second line regimen is established although small retrospective series suggest that chemotherapy may be active in selected patients. We present results of a large retrospective series of patients undergoing second-line chemotherapy at institutions across the UK that use the ABC-02 standard of Cisplatin and Gemcitabine (CisGem) as first-line treatment. Methods Patients with ABC, previously treated with CisGem and who went on to receive second-line chemotherapy, were identified from institutional databases. Demographic data, response and survival outcome measures were collected according to an agreed proforma. Results Sixty-three eligible patients (median age: 61.6 years (range: 39.8 – 78.3 years)) were identified between Feb 2007 and Feb 2011, from 9 centres. Patients were treated mostly with a platinum based regimen (n = 42), either a re-challenge of CisGem (n = 17), an oxaliplatin/ infused 5-FU regimen (mFOLFOX, n = 17) or oxaliplatin with capecitabine (n = 4). Most patients had a performance status of 0 or 1. A median PFS of 4.0 months (95% CI: 3.3 – 5.6 months) and an OS of 8.1 months (95% CI: 5.3 – 11.4 months) following second line therapy were demonstrated. Patients had an overall OS of 19.5 months (95% CI: 17.0 – 25.2 months) from the start of first-line therapy; this compares with a median OS of 11.7 months from the ABC-02 study. Conclusions Use of second-line chemotherapy in advanced BTC is of potential benefit. These data, although retrospective, suggests there is a population suitable for second-line, prospective randomised studies with chemotherapy or targeted agents and provide baseline outcome data with which to statistically design such studies. Updated data will be shown. Disclosure All authors have declared no conflicts of interest.

4636 Background: Pre-clinical evidence demonstrates that the human Cholecystokinin-2 receptor antagonist Z-360, can inhibit pancreatic tumour growth and prolong survival when combined with gemcitab...