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4015 Background: PLATFORM is a prospective, open-label, multicentre, adaptive phase II trial assessing maintenance therapy in patients (pts) with OG adenocarcinoma after platinum-based first-line induction chemotherapy. HER2 negative pts were initially randomised 1:1:1:1:1 to surveillance (A1), capecitabine (A2), durvalumab (A3), with rucaparib (A4) and capecitabine + ramucirumab (A5) added later as per adaptive design. Here we report the primary analysis of durvalumab maintenance vs. surveillance. Methods: Pts were randomised upon achieving response or stable disease following 18 weeks of platinum-based chemotherapy and were stratified by region, disease extent and performance status. A1 pts had 4 weekly surveillance visits and A3 pts received 10mg/kg durvalumab iv Q2W. Target accrual was 154 pts/arm; however, A3 was closed prematurely after cessation of industry support. The primary endpoint was progression-free survival (PFS) from randomisation post induction chemotherapy to disease progression according to RECIST 1.1 criteria, or death. Secondary endpoints were time to treatment failure (TTF), objective response rate (ORR), overall survival (OS) and toxicity. Survival analyses according to PD-L1 using the combined positive score (CPS, Ventana SP263 assay) was conducted. Results: A total of 205 pts were concurrently randomised into A1 (n = 100) and A3 (n = 105). At data cut-off (02 Feb 2021), median follow up was 24.2 months [95% confidence interval (CI) 21.6-36.8]. There was no significant difference in PFS between A1 and A3 [median PFS: 3.2 vs. 4.7 months (hazard ratio (HR) 0.79 (95% CI 0.59-1.06, p = 0.122) respectively]. Median OS was 11.4 vs. 11.3 months (HR 0.92, 95% CI 0.66-1.27, p = 0.60) in A1 and A3 respectively and no significant difference in TTF was detected between both arms (median TTF: 3.2 vs. 3.5 months (HR 0.92, 95% CI 0.69-1.23, p = 0.558)]. ORR was 6% in A3 (n = 2 complete and n = 4 partial responses) whereas no radiological responses were seen in A1. PD-L1 results were available for 76 pts in A1 and 77 pts in A3. PFS was comparable between subgroups using the PD-L1 CPS thresholds of ≥1, ≥5 and ≥10. The safety population consisted of 199 pts (A1: 98 pts and A3: 101 pts). Grade ≥3 treatment-related adverse events were reported in 18% of A3 pts and no new safety signals were identified. Conclusions: Although a survival advantage was not seen with maintenance durvalumab compared to surveillance, a subset of patients who received durvalumab demonstrated incremental radiological responses. Exploratory analysis of PD-L1 expression was not associated with improved survival outcomes. Clinical trial information: NCT02678182.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer death in the UK. Its poor prognosis is attributed to late detection and limited therapeutic options. Expression of SULF2, an endosulfatase that modulates heparan sulfate proteoglycan 6-O-sulfation and is reportedly tumourigenic in different types of cancer, was investigated. Methods: SULF2 expression was determined immunohistochemically in archival surgical resection tissue sections from 93 patients with a confirmed histological diagnosis of PDAC between 2002 and 2008 followed for a median of 9 years. Relationships with clinico-pathological parameters and patient survival were explored. Results: The majority of PDACs showed positive SULF2 staining in tumour cells and intratumoural or tumour-adjacent stroma. Greater than 25% SULF2-positive tumour cells was present in 60% of cancers and correlated with tumour stage (P=0.002) and perineural invasion (P=0.024). SULF2 intensity was scored moderate or strong in 81% of cancers and positively correlated with vascular invasion (P=0.015). High SULF2 expression, defined as >50% SULF2-positive tumour cells and strong SULF2 staining, was associated with shorter time to radiological progression (P=0.018, HR 1.98, CI 1.13–3.47). Similarly, by multivariate analysis, high SULF2 expression was independently associated with poorer survival (P=0.004, HR 2.10, CI 1.26–3.54), with a median survival of 11 months vs 21 months for lower PDAC SULF2. Conclusions: Elevated SULF2 in PDAC was associated with advanced tumour stage, vascular invasion, shorter interval to radiological progression and shorter overall survival. SULF2 may have roles as a prognostic biomarker and as a therapeutic target for patients with PDAC.

282 Background: Advanced OGA patients (pts) are treated with platinum-based 1st line chemotherapy but the role of maintenance therapy once disease control is obtained is unknown. Methods: PLATFORM is a prospective, open-label, adaptive phase II trial assessing maintenance therapy in OGA. HER2 negative pts with advanced OGA achieving response or stable disease on completion of 1st line platinum-based chemotherapy were initially randomised to surveillance (A1), capecitabine (A2) and durvalumab (A3). Rucaparib (A4) and capecitabine+ramucirumab (A5) were subsequently added as part of adaptive design. Primary endpoint is progression-free survival with target recruitment of 154pts/arm. A pre-planned futility interim analysis (IA) is triggered when 61 pts/arm are recruited and evaluable using 12-week progression-free rate (PFR). Individual arms will continue accrual if the upper limit of 1-sided 95% CI difference is > 0 when compared to A1. Biomarker analyses of A1 and A3 IA patients include: PDL1 as tumour and immune cell combined proportion (TIP), multiplex IHC of tumour infiltrating lymphocytes (TILs), TMB and MSI status by whole exome sequencing. Results: To date, 1053 pts have registered prior to or during 1st line therapy and 356 pts randomised. Primary attrition was due to disease progression. Baseline demographics in the IA population (arms A1 to A3, n = 183) were male (81%); median age 65 yrs; metastatic disease (92%); oesophageal (40%), OG junction (28%) and gastric (32%) primary. 12-week PFR were A1: 51% (95%CI: 38-64%); A2: 52% (95%CI: 40-65%); A3: 49% (95%CI: 36-62%). PFR differences to arm A1 were A2: 1.6% (95%CI: -13.2 to 16.5%); A3: -1.6% (95%CI: -16.5 to 13.3%). In A1, PFR was 53% vs 43% in PDL1 TIP < 10% and ≥10% respectively. In A3, PFR was 51% vs 100% in PDL1 TIP < 10% and ≥10% respectively. 3 pts in A3 had partial response; none were seen in A1 and A2. Density of TILs subsets, TMB and MSI data will be presented. Conclusions: PLATFORM IA did not indicate futility in maintenance capecitabine or durvalumab compared to surveillance in advanced OGA and will continue to target accrual. Incremental radiological responses were observed with maintenance durvalumab only. Clinical trial information: NCT02678182.

4022 Background: No large scale randomised data exists evaluating the impact of age and sex in patients (pts) undergoing potentially curative surgery and CTx for OG cancer. However, differences in age and sex may be contributing factors to variability in CTx dose-response and toxicity which could also impact survival. Methods: Data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival data, hazard ratios were calculated for pts

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.

Oral capecitabine (Xeloda®) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.

Background: The monoclonal antibody 3H1 mimics the external structure of the carcinoembryonic antigen (CEA). It therefore has the potential, via the anti-idiotypic network, to stimulate immune responses to CEA that may benefit colorectal cancer patients. Patients and methods: A total of 630 patients with previously untreated metastatic colorectal cancer were randomised in a 2:1 fashion to receive bolus 5-fluorouracil (5-FU) and leucovorin (LV) plus either 3H1 (n = 422) or placebo (n = 208). Results: The addition of 3H1 to 5-FU and LV did not result in increased toxicity. Survival for the full intent-to-treat population was 14.7 months for the 3H1 arm and 15.2 months for the placebo arm (P = 0.80). Anti-CEA antibody responses were observed in 70% of patients treated with 3H1. Patients with a negative CEA response had a median survival of 8.3 months (95% CI 7.5–11.0) compared with patients with a strong response: median survival not reached (P

Summary Background We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer. Methods TeloVac was a three-group, open-label, randomised phase 3 trial. We recruited patients from 51 UK hospitals. Eligible patients were treatment naive, aged older than 18 years, with locally advanced or metastatic pancreatic ductal adenocarcinoma, and Eastern Cooperative Oncology Group performance status of 0–2. Patients were randomly assigned (1:1:1) to receive either chemotherapy alone, chemotherapy with sequential GV1001 (sequential chemoimmunotherapy), or chemotherapy with concurrent GV1001 (concurrent chemoimmunotherapy). Treatments were allocated with equal probability by means of computer-generated random permuted blocks of sizes 3 and 6 in equal proportion. Chemotherapy included six cycles of gemcitabine (1000 mg/m 2 , 30 min intravenous infusion, at days 1, 8, and 15) and capecitabine (830 mg/m 2 orally twice daily for 21 days, repeated every 28 days). Sequential chemoimmunotherapy included two cycles of combination chemotherapy, then an intradermal lower abdominal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF; 75 μg) and GV1001 (0·56 mg; days 1, 3, and 5, once on weeks 2–4, and six monthly thereafter). Concurrent chemoimmunotherapy included giving GV1001 from the start of chemotherapy with GM-CSF as an adjuvant. The primary endpoint was overall survival; analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN4382138. Findings The first patient was randomly assigned to treatment on March 29, 2007, and the trial was terminated on March 27, 2011. Of 1572 patients screened, 1062 were randomly assigned to treatment (358 patients were allocated to the chemotherapy group, 350 to the sequential chemoimmunotherapy group, and 354 to the concurrent chemoimmunotherapy group). We recorded 772 deaths; the 290 patients still alive were followed up for a median of 6·0 months (IQR 2·4–12·2). Median overall survival was not significantly different in the chemotherapy group than in the sequential chemoimmunotherapy group (7·9 months [95% CI 7·1–8·8] vs 6·9 months [6·4–7·6]; hazard ratio [HR] 1·19, 98·25% CI 0·97–1·48, p=0·05), or in the concurrent chemoimmunotherapy group (8·4 months [95% CI 7·3–9·7], HR 1·05, 98·25% CI 0·85–1·29, p=0·64; overall log-rank of χ 2 2df =4·3; p=0·11). The commonest grade 3–4 toxic effects were neutropenia (68 [19%] patients in the chemotherapy group, 58 [17%] patients in the sequential chemoimmunotherapy group, and 79 [22%] patients in the concurrent chemoimmunotherapy group; fatigue (27 [8%] in the chemotherapy group, 35 [10%] in the sequential chemoimmunotherapy group, and 44 [12%] in the concurrent chemoimmunotherapy group); and pain (34 [9%] patients in the chemotherapy group, 39 [11%] in the sequential chemoimmunotherapy group, and 41 [12%] in the concurrent chemoimmunotherapy group). Interpretation Adding GV1001 vaccination to chemotherapy did not improve overall survival. New strategies to enhance the immune response effect of telomerase vaccination during chemotherapy are required for clinical efficacy. Funding Cancer Research UK and KAEL-GemVax.

BACKGROUND:Second-line chemotherapy for patients with oesophagogastric adenocarcinoma refractory to platinum and fluoropyrimidines has not shown benefits in health-related quality of life (HRQoL). We assessed whether the addition of docetaxel to active symptom control alone can improve survival and HRQoL for patients.METHODS:For this open-labelled, multicentre trial, we recruited patients aged 18 years or older from 30 UK centres. Patients were eligible if they had an advanced, histologically confirmed adenocarcinoma of the oesophagus, oesophagogastric junction, or stomach that had progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination. Patients could have an Eastern Cooperative Oncology Group performance status of 0-2. We randomly assigned patients using a central, computerised minimisation procedure to receive docetaxel plus active symptom control, or active symptom control alone (1:1; stratified by disease status, disease site, duration of response to previous chemotherapy, and performance status). Docetaxel was given at a dose of 75 mg/m(2) by intravenous infusion every 3 weeks for up to six cycles. The primary endpoint was overall survival, analysed by intention to treat. This is the report of the planned final analysis. This study is an International Standardised Randomised Controlled Trial, number ISRCTN13366390.FINDINGS:Between April 21, 2008, and April 26, 2012, we recruited 168 patients, allocating 84 to each treatment group. After a median follow-up of 12 months [IQR 10-21]) and 161 (96%) deaths (80 in the docetaxel group, 81 in the active symptom control group), median overall survival in the docetaxel group was 5.2 months (95% CI 4.1-5.9) versus 3.6 months (3.3-4.4) in the active symptom control group (hazard ratio 0.67, 95% CI 0.49-0.92; p=0.01). Docetaxel was associated with higher incidence of grade 3-4 neutropenia (12 [15%] patients vs no patients), infection (15 [19%] patients vs two [3%] patients), and febrile neutropenia (six [7%] patients vs no patients). Patients receiving docetaxel reported less pain (p=0.0008) and less nausea and vomiting (p=0.02) and constipation (p=0.02). Global HRQoL was similar between the groups (p=0.53). Disease specific HRQoL measures also showed benefits for docetaxel in reducing dysphagia (p=0.02) and abdominal pain (p=0.01).INTERPRETATION:Our findings suggest that docetaxel can be recommended as an appropriate second-line treatment for patients with oesophagogastric adenocarcinoma that is refractory to treatment with platinum and fluoropyrimidine.FUNDING:Cancer Research UK.

The administration of current cancer chemotherapy agents is associated with significant toxicity and makes these agents ideal candidates for more selective drug targeting. Polymer prodrug therapy is a strategy that provides a means of targeting cytotoxic agents to specific organs or tumour tissues. The principle structure of a polymer prodrug consists of a water soluble polymeric carrier or backbone, linked to the chemotherapeutic drug of choice. The modification of a specific anticancer drug in this way can theoretically allow specific tumour targeting, thus protecting normal cells and allowing higher doses of the drug to be administered whilst reducing the potential toxicity profile.

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.

Purpose Data concerning the prevalence of and outcomes related to thromboembolic events (TEs) in patients with advanced gastroesophageal cancer who are undergoing chemotherapy are limited. Patients and Methods This was a prospective, exploratory analysis of TEs in a randomized, controlled trial of 964 patients recruited between 2000 and 2005 and treated with epirubicin/platinum/fluoropyrimidine combination chemotherapy for advanced/locally advanced gastroesophageal cancer. Regimens were epirubicin (E), cisplatin (C), fluorouracil (F; ECF); E, C, capecitabine (X; ECX); E, F, oxaliplatin (O; EOF); and EOX. Continuously infused F was administered via a central venous access device (CVAD) with 1 mg of warfarin for thromboprophylaxis. The principal outcome was the incidence of TEs (venous and arterial) in the whole treated patient cohort, according to chemotherapy, associated with CVADs and TE-related prognoses. Results The incidences of any, of venous, and of arterial TEs among 964 treated patients were 12.1% (95% CI, 10.7 to 14.3), 10.1% (95% CI, 8.3 to 12.3), and 2.2% (95% CI, 1.4 to 3.4) respectively. There were fewer TEs in the O compared with the cisplatin groups (EOF/EOX v ECF/ECX: 7.6% v 15.1%; P = .0003). C was identified as a risk factor for TE in multivariate analysis (hazard ratio [HR], 0.51; 95% CI, 0.34 to 0.76; P = .001). There was no difference in the incidence of TEs for the F group compared with the capecitabine groups. The incidence of CVAD-related thrombosis was 7.0% (ECF/EOF arms). Overall survival was worse for patients who experienced TEs versus no TEs (median survival, 7.4 v 10.5 months; HR, 0.8; 95% CI, 0.64 to 0.99; P = .043). Conclusion This analysis has prospectively quantified the incidence/pattern of TEs among patients with advanced gastroesophageal cancer who were treated with four triplet regimens, has demonstrated a differential thrombogenic effect according to platinum use, and has noted a poorer outcome associated with TE during treatment. Chemotherapy-related TE should contribute to the risk/benefit assessment of treatment.

surgery occurred in 3(5.6%) and 4(7.4%) patients in the CT group versus 4(7.8%) and 3(5.9%) patients in the CRT group. Conclusions: Part 1 of the TOPGEAR trial demonstrates preoperative CRT to be safe and feasible. With IDSMC recommendation the trial has proceeded to Part 2 where overall survival will be the primary end point. Current accrual is 170 patients recruited from 55 active sites. No conflict of interest.

4002 Background: Neoadjuvant chemotherapy (2 cycles cisplatin/5 fluorouracil) (CF) followed by surgery is a standard of care for locally advanced oesophageal cancer. We investigated whether more ch...

Purpose: The role of adjuvant chemotherapy in early-stage epithelial ovarian cancer (EOC) has been controversial. We have previously reported the cases of patients managed with a policy of observation only. We now present the salvage rate for the patients in that study who experienced relapse. Patients and Methods: One hundred ninety-four patients with stage I EOC presenting between 1980 and 1994 received no adjuvant chemotherapy, but were treated with platinum-based chemotherapy at relapse. We calculated the progression-free survival (PFS) and overall survival (OS) for the whole cohort and the salvage rate for those who experienced relapse. We defined salvage as freedom from relapse for 5 years after platinum treatment. Results: Sixty-one (31%) of 194 patients experienced relapse, and 55 received platinum-based chemotherapy. Twenty-four percent were progression-free at 5 years after this treatment. Clear-cell histology and cyst rupture before the patients’ original surgery were independent prognostic factors for PFS after salvage chemotherapy. The OS for all 194 patients is 72% at 10 years (median follow-up, 8.7 years), with an 80% disease-specific survival (DSS). Conclusion: We have shown that some patients with stage I EOC can be successfully treated with a salvage chemotherapy regimen after a policy of observation only. Interestingly, approximately 30% of stage I patients who die within 10 years do so from causes other than EOC (OS, 72%; DSS, 80%). Our findings need to be taken into consideration when the results from recent randomized trials of adjuvant chemotherapy in this patient population (International Collaborative Ovarian Neoplasm Trial 1/European Organization for Research and Treatment of Cancer Adjuvant Chemotherapy in Ovarian Neoplasm Trial) are being discussed with patients.

4121 Background: The TeloVac trial randomized 1,062 patients with advanced pancreatic cancer to a control chemotherapy Arm1, using GemCap; sequential chemoimmunotherapy Arm 2, GemCap for 8 wks foll...

4067 Background: REAL3 evaluated EOC + P in advanced oesophago-gastric adenocarcinoma. We previously reported that addition of P was associated with increased diarrhoea, skin rash and mucositis wit...

91 Background: The REAL3 trial evaluated the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. We previously reported that addition of panitumumab was not associated with improvement in survival endpoints. In this analysis we aimed to explore factors associated with OS in the REAL3 population. Methods: Analysis performed in ITT population (n=553). OS was evaluated in relation to the baseline characteristics displayed in the table below. Cox regression was used to obtain HRs and 95% CIs. Factors with p100 U/L. Results: Results of the univariate analysis are shown in the table below. In multi-variate analysis, the factors which remained statistically significant for OS were: PS (p=0.080): 1 vs 0 HR 1.24 (95% CI 0.99-1.57); 2 vs 0 HR 1.57 (95%CI 0.97-2.54) Disease extent (p=0.054): Met disease vs LA HR 1.42 (95% CI 0.99-2.02) Baseline global health score (p=0.005): Low vs high HR 1.52 (95% CI 1.16-2.00); middle vs high HR 1.45 (95% CI 1.11-1.89) Patients with an RMH Prognostic Index score of 0 (good prognosis) had median OS of 13.1 mo. This compared to 9.5 mo in patients with 1-2 adverse features (intermediate prognosis) (HR 1.37, 95% CI 1.12-1.68; p=0.002) and 4.7 mo in patients with 3-4 adverse features (poor prognosis) (HR 4.02, 95% CI 1.96-8.22; p

4023 Background: Survival in patients who relapse after first-line chemotherapy (CT) for advanced esophago-gastric adenocarcinoma (EGC) is poor though recently randomised trials (RCT) have suggested a small benefit for second line chemotherapy with taxanes or irinotecan. There is very little data on health related quality of life (HRQL) or overall survival (OS), particularly in patients who progress shortly after first-line therapy. Methods: COUGAR-02 was a multicentre open-label, phase III RCT for patients with locally advanced or metastatic EGC of performance status (PS) 0-2 who had progressed within 6 months of previous platinum/fluoropyrimidine CT. Patients were randomised (1:1) to receive either docetaxel 75mg/m2every 3 weeks for up to 6 cycles or active symptom control (ASC). The primary endpoint was OS. The secondary endpoint of HRQL, assessed using EORTC QLQ-C30 and QLQ-ST022, was analysed using standardised area under a curve and compared using Wilcoxon rank sum test. Sensitivity analysis adjusting for dropouts due to death were performed using quality adjusted survival. Results: 168 patients (84 patients in each arm) were recruited between April 2008 and April 2012. Median age was 65 years (range 28-84); 81% were males. PS at randomisation was 0 for 27%, 1 for 57% and 2 for 15%. 86% had metastatic disease. 43% progressed during previous CT, 28% progressed within 3 months of end of previous CT and 29% progressed between 3 and 6 months. Median number of cycles of docetaxel was 3. 23% completed 6 cycles. Docetaxel was well tolerated and resulted in a significantly improved OS over ASC alone (HR=0.67 (95% CI 0.49-0.92); p=0.01). Objective response rate was 7%. For QLQ-C30, patients on docetaxel arm reported significantly less pain (p=0.0008) and trend for less nausea and vomiting (p=0.02) and constipation (p=0.02) than those on ASC arm. Similar global HRQL seen (p=0.53).For QLQ-ST022, trend seen for less dysphagia (p=0.02) and pain symptoms (p=0.01) for patients on docetaxel arm than ASC Conclusions: Docetaxel provided a significant OS benefit over ASC with improvements in symptom scores and no loss in overall HRQL. Docetaxel can be considered a standard of care in this setting. Clinical trial information: NCT00978549.

TPS4156 Background: Perioperative ECX chemotherapy is a standard of care for localised operable gastric/OGJ/lower oesophageal adenocarcinoma (Cunningham, NEJM 2006). In combination with chemotherapy B, a monoclonal antibody targeting VEGF-A, results in improved response rates (RR) and progression free survival in advanced gastric cancer (Ohtsu, JCO 2011). ST03 aims to assess the safety and feasibility (stage I, 200 pts) and efficacy (stage II) of the addition of B to perioperative ECX chemotherapy. Methods: ST03 is a multicentre, open-label, phase II/III randomised trial open at 106 UK centres. Eligibility criteria are histologically proven, untreated, resectable, lower oesophageal, OGJ or gastric adenocarcinoma; age ≥18 years; WHO PS 0-1; and adequate cardiac ejection fraction (EF). Exclusion criteria are TIA/CVA or MI ≤1 year; uncontrolled hypertension; ≥ Grade 2 NYHA heart failure; recent gastrointestinal inflammatory conditions or major surgery/trauma/open biopsy

LBA4004 Background: GV1001, a promiscuous class II epitope encompassing aa 611-626 of hTERT led to the development of CD4+ clones recognizing hTERT in patients with advanced pancreatic cancer (APC). Preclinically gemcitabine increases antigen cross-presentation, enhances T cell trafficking/activation, and reduces MDSCs and Tregs. Methods: Patients with APC were randomized 1:1:1 to: Arm 1 GemCap; 2 GemCap for 8/52 followed by GV1001 followed by further GemCap if no PD at week 8; 3 concurrent administration of GemCap and GV1001. 735 (69.2%) had metastatic disease and 948 (89.3%) had ECOG PS=0 or 1. Randomization was stratified by stage and PS. Primary endpoint was overall survival (OS); secondary endpoints included ORR, TTP, and AEs. Recruitment target was 1,110 patients (780 deaths) to permit detection of a hazard ratio of 0.748 between either GV1001 arm and Arm 1 using a 2-sided α=0.025 level of significance with at least 80% power. Results: 1,062 pts from 51 centers were randomized. Trial maturity was high (72.7% patients died): median follow-up was 6.11 months. The overall response rates were Arm 1=17.6%; Arm 2=8.9% (p=0.001); Arm 3: 15.5% (p=0.460 compared with Arm 1). Conclusions: OS with concurrent GemCap/GV1001 was not different to that with GemCap alone. OS with sequential GV1001 was not statistically different to GemCap alone as it did not meet the criterion for statistical significance (p

LBA4 Background: Survival in patients who relapse after first-line chemotherapy for advanced esophagogastric adenocarcinoma (OGC) is poor though recently randomized trials have suggested a small survival benefit for second-line chemotherapy with taxanes or irinotecan. There is very little data on quality of life or survival, particularly in patients who progress shortly after first-line therapy. Methods: COUGAR-02 was a multicenter open-label, randomized controlled phase III trial for patients with locally advanced or metastatic OGC of performance status (PS) 0-2 who had progressed within 6 months of previous platinum/fluoropyrimidine (PF) chemotherapy (CT). Patients were randomized (1:1) to receive either docetaxel 75mg/m2every 3 weeks for up to 6 cycles or active symptom control (ASC), which could include any treatment thought by the treating clinician to be appropriate for the management of symptoms including radiotherapy, steroids and supportive medications. The primary endpoint was overall survival. Secondary endpoints were response rate, toxicity, health related quality of life (HRQL) and healthcare resource use. Results: Between April 2008 and April 2012, 168 patients were recruited (84 patients in each arm). Median age was 65 years (range 28-84), 81% were male. PS at randomisation was 0 for 27%, 1 for 57% and 2 for 15%. Site of disease was stomach in 46%, esophagogastric junction in 34% and esophagus in 20%. 86% had metastatic disease. 43% progressed during previous CT, 28% progressed within 3 months of end of previous CT and 29% progressed between 3 and 6 months. 19 (23%) patients completed 6 CT cycles (median 3 cycles per patient). The main reasons for not completing treatment were progression and toxicity. Docetaxel significantly improved overall survival over ASC alone (median 5.2 months (95% CI 4.1-5.9 months) for docetaxel; 3.6 months (95% CI 3.3-4.4 months) for ASC, HR=0.67 (95% CI 0.49-0.92); p=0.01). 7% had a partial response and 46% had stable disease after CT. 21% on docetaxel had grade 4 toxicity. Conclusions: The addition of docetaxel to ASC significantly improved overall survival. Docetaxel can be considered a standard of care in this setting. Clinical trial information: 13366390.

LBA4000 Background: EGFR overexpression occurs in 27-50% of esophagogastric adenocarcinomas (OGA), and correlates with poor prognosis. The REAL3 trial evaluated the addition of the anti-EGFR antibody panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. Methods: Patients with untreated, metastatic or locally advanced OGA were randomised to EOC (E 50mg/m2, O 130mg/m2, C 1250mg/m2/day) or mEOC+P (E 50mg/m2, O 100mg/m2, C 1000mg/m2/day, P 9mg/kg). Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), response rate (RR), toxicity, and biomarker evaluation. Response was evaluated by RECIST after 4 and 8 cycles. Following IDMC review in October 2011 trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. Results: 553 patients were recruited (EOC 275, mEOC+P 278), with median follow-up 5.0 and 5.2 months respectively. Median OS was 11.3 months with EOC compared to 8.8 months with mEOC+P (HR 1.37: 95% CI 1.07-1.76, p=0.013). Median PFS was 7.4 and 6.0 months respectively (HR 1.22: 95% CI 0.98-1.52, p=0.068), with RR being 42% compared to 46% (odds ratio 1.16: 95% CI 0.81-1.57, p=0.467). mEOC+P was associated with ↑ G3/4 diarrhoea (17% vs 11%), skin rash (14% vs 1%) and thrombotic events (12% vs 7%), but ↓ haem toxicity (>G3 neutropenia 14% vs 31%). In the mEOC+P arm, OS was significantly improved in patients with G1-3 rash (77%, n=209) on treatment compared to those without (23%, n=63); median OS 10.2 vs 4.3 months (p

LBA4006 Background: The effect of adjuvant treatment on overall survival (OS) of resected ampullary adenocarcinoma is not known. The aim was to compare the survival effect of adjuvant chemotherapy compared to observation (OBS) after resection and within the chemotherapy group to compare 5-fluorouracil/folinic acid (5-FU/FA) against gemcitabine (GEM). Methods: Patients were stratified by R0/R1 margins, randomised into three arms: (1) 5-FU/FA (FA, 20 mg/m2 iv bolus then 5-FU, 425 mg/m2, iv bolus, 1-5d every 28 days); (2) GEM (100mg/m2 iv infusion 1d, 8d and 15d every 4 weeks); (3) observation. The primary outcome measure was OS of chemotherapy versus no chemotherapy. 300 patients (200 chemotherapy and 100 observation) would provide 80% power to detect a 15% 5y survival difference, p

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 ...

4019 Background: Perioperative chemotherapy is a standard of care for localised oesophagogastric cancer. B is a monoclonal antibody targeting vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis. Tumour VEGF expression and high preoperative serum VEGF are independent predictors of poor prognosis for resected gastric cancer. ST03 is an ongoing randomised phase II/III trial of perioperative ECX ± B in pts with operable gastric or OGJ adenocarcinoma. Methods: Pts receive 3 preoperative and 3 postoperative ECX ± B 7.5 mg/kg, then 6 × maintenance B in the experimental arm only. The Independent Data Monitoring Committee undertook a preplanned review of preliminary safety data relating to preoperative chemotherapy and surgery for the first 104 pts. We present these data here to reassure clinicians and patients involved in the trial. Results: 43 ECX and 42 ECX + B pts have completed preoperative chemotherapy, 38 (88%) and 37 (88%) respectively received all 3 cycles. Of the 10 pts who rece...

LBA4017 Background: The aim was to establish the potential use of the third generation platinum compound, oxaliplatin (O) & the oral fluoropyrimidine capecitabine (X) in untreated patients (pts) with advanced OG cancer. Methods: After stratification for PS and extent of disease, pts with histologically confirmed adenocarcinoma, squamous or undifferentiated carcinoma of the oesophagus, oesophago-gastric junction or stomach were randomised, in a 2 x 2 design, to 1 of 4 regimens; epirubicin, cisplatin, fluorouracil (ECF), EOF, ECX or EOX. Doses E 50 mg/m2, C 60 mg/m2 & O 130 mg/m2 IV 3 weekly; F 200 mg/m2 IV daily & X 625 mg/m2 twice daily PO continuously; for 8 cycles. The primary endpoint was overall survival. With 1000 pts (250 per arm) the study had 80% power to demonstrate non-inferiority of X over F and also O over C if the upper limit of the HR 95% CI excluded 1.23 (α = 0.05) in the per protocol population. Analysis was performed using the logrank test and Cox regression analysis. Results: 1002 pts were randomised from 61 centres. Demographics were balanced, 89% were PS 0–1, 77% metastatic, median age 63 (range 22–83), 81% were male and 40% gastric primaries. Histology: adenocarcinoma in 88% and 52% poorly differentiated. 11 pts were ineligible and 27 pts were withdrawn before treatment commenced. Median follow up was 17.1 months and 850 events have occurred. There were no significant differences in response rates comparing ECF to, EOF, ECX and EOX (41%, 42%, 46%, and 48% respectively); grade 3–4 non haematological toxicity 36%, 42%, 33% and 45%; and grade 3–4 neutropaenia 42%, 30% (p = 0.008), 51% (p = 0.043) and 28% (p = 0.001) respectively. Conclusions: Capecitabine may replace 5FU and Oxaliplatin may replace Cisplatin in triplet regimens used for the treatment of advanced OG cancer. [Table: see text] [Table: see text]

3737 Background: The improved safety profile of the oral fluoropyrimidine X (Xeloda) versus bolus 5-FU/LV has been demonstrated in over 3000 pts in 3 large randomized trials in 1st line metastatic and adjuvant colon cancer (Twelves EJC 2002, Scheithauer Ann Oncol 2003). In addition, the safety advantage over 5-FU/LV in the adjuvant setting was maintained in older pts (≥65 years) and also in terms of less early severe toxicity with X. The median age of pts at diagnosis of colon cancer is increasing in developed countries. Therefore we examined whether there is enough evidence to support the safe use of X in an elderly population, i.e. pts 70 years and older. Methods: We performed retrospective analyses on the safety database of the X-ACT adjuvant colon cancer trial, which compared X (993 pts) to 5-FU/LV Mayo Clinic Regimen (974 pts) in Dukes' C colon cancer pts. Adverse events (AEs) in the two arms were analyzed by age

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...