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It is well recognized that the primary KIT or PDGFRA variant of a gastrointestinal stromal tumour (GIST) can predict sensitivity to imatinib. However, these data are currently spread across a wide range of publications and have not been collated as one reference. A broad-ranging literature search was therefore performed to assemble such a database which should help optimize imatinib-based management of GIST patients henceforth. Having excluded wild type GISTs and results for imatinib used as adjuvant therapy, 79 publications (dated August 2001 to March 2022) underwent data extraction. These data on imatinib sensitivity were either derived from in vitro studies, predicted by in silico analysis or based on in vivo clinical patient response. Data interpretation carried some caveats: there was a potential for replication of patient-derived data between older and new publications; only predicted protein sequences were presented; the criteria used to record clinical response were not uniform across all publications; and imatinib dosage could vary between different clinical publications. However, these data showed broad agreement of imatinib sensitivity amongst similar subtypes of KIT or PDGFRA variant. There was also agreement between in vivo versus in vitro/in silico derived sensitivity data for most variants when both data types were available.

Paediatric dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue malignant tumour which displays aggressive local behaviour and has low metastatic potential. The diagnosis is often delayed as DFSP is usually mistaken for other skin conditions, particularly in the early stages of disease. DFSP tends to follow an indolent course after the initial presentation with what is often described as a "rubbery lump". As the disease progresses, the lump tends to enlarge, change colour, and exhibit a more nodular consistency. In rare cases, DFSP can present as an ulcerated exophytic lesion or a depressed area of skin, making diagnosis even more challenging. A high index of suspicion is warranted for early diagnosis, and referral to a specialist unit with expertise in both oncologic resection and reconstruction. DFSP tumours arise from the dermis and grow with finger-like projections. Therefore, in cosmetically sensitive or functionally important locations, an excision and analysis technique that assesses all excision margins is the gold standard of care. Slow Mohs technique performed with en bloc excision is a well-tolerated option for oncologic resection of the tumour. Mohs technique can also be considered but can be challenging in children for reasons explained below. As an alternative, depending on the anatomical location, tumours can be excised with a wide local excision. While an excision technique that incorporates the deep fascia with a 3-cm peripheral margin is acceptable in adults, planning of the excision margin in children should involve consideration of preoperative imaging with MRI, site of the tumour, age, and physical built of the child. Patients should be offered all treatment options considering the local outcomes, available expertise, and cost. A multidisciplinary approach and good communication between team members is crucial. Close collaboration with a pathologist who is familiar with sectioning technique that allows margin control is of paramount importance. Soft tissue reconstruction should be performed immediately after oncologic clearance, although a staged approach may be required. Adjuvant radiotherapy should be avoided in children due to the long-term risk of secondary malignancies and potential for growth disruption.

The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke1–3. As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug–biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy—including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug–biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke. Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

Objectives To describe rates of confirmed and suspected neutropenic sepsis (NS) and associated hospital resource utilisation in patients with non-small cell lung cancer (NSCLC) treated with docetaxel monotherapy following relapse after ≥1 line of chemotherapy in routine UK clinical practice. Materials and methods A multi-centre, retrospective, observational research study was conducted in seven centres across England and Wales. Adult patients with stage III/IV NSCLC initiated on docetaxel monotherapy between 2010 and 2016 in routine clinical practice (aged ≥18 years at initiation) following failure of first-line chemotherapy were eligible. Data were collected from hospital medical records between May 2016 and July 2016, on all episodes of confirmed or suspected NS related to docetaxel monotherapy, including patient characteristics. Episodes of confirmed NS were defined as documented absolute neutrophil count 9 /L, plus temperature >38 °C or other signs/symptoms of sepsis, otherwise episodes were classified as suspected NS. Results 121 patients were included (median age 65.5 years; 57.9% male; median 4.0 cycles of docetaxel; 19.8% treated with prophylactic granulocyte-colony stimulating factor). Episodes of confirmed or suspected NS were recorded in 21/121 (17.4%) patients (11 confirmed episodes in 11 [9.1%] patients and 11 suspected episodes in 10 [8.3%] patients). Resource utilisation data were available for 21/22 episodes; the mean length of stay for confirmed NS admissions (n = 11) was 9.2 (SD: 9.2) days and for suspected NS admissions (n = 10) was 4.7 (SD: 4.6) days. The most commonly prescribed treatment for NS was piperacillin/tazobactam therapy (46.5% of all documented treatments). The mean total costs of managing patients with confirmed NS (n = 11) and suspected NS (n = 9) were £3163 (SD: £2921) and £1790 (SD: £1585) per patient, respectively. Conclusion Rates of confirmed NS in UK clinical practice were broadly similar to those reported in clinical trials; however, the burden of suspected NS, not routinely reported elsewhere, is also substantial.

Background: Alveolar soft-part sarcoma (ASPS) is a rare soft-tissue sarcoma that is unresponsive to chemotherapy. Cediranib, a tyrosine-kinase inhibitor, has shown substantial activity in ASPS in non-randomised studies. The Cediranib in Alveolar Soft Part Sarcoma (CASPS) study was designed to discriminate the effect of cediranib from the intrinsically indolent nature of ASPS. Methods: In this double-blind, placebo-controlled, randomised, phase 2 trial, we recruited participants from 12 hospitals in the UK (n=7), Spain (n=3), and Australia (n=2). Patients were eligible if they were aged 16 years or older; metastatic ASPS that had progressed in the previous 6 months; had an ECOG performance status of 0–1; life expectancy of more than 12 weeks; and adequate bone marrow, hepatic, and renal function. Participants had to have no anti-cancer treatment within 4 weeks before trial entry, with exception of palliative radiotherapy. Participants were randomly assigned (2:1), with allocation by use of computer-generated random permuted blocks of six, to either cediranib (30 mg orally, once daily) or matching placebo tablets for 24 weeks. Treatment was supplied in number-coded bottles, masking participants and clinicians to assignment. Participants were unblinded at week 24 or sooner if they had progression defined by Response Evaluation Criteria in Solid Tumors (version 1.1); those on placebo crossed over to cediranib and all participants continued on treatment until progression or death. The primary endpoint was percentage change in sum of target marker lesion diameters between baseline and week 24 or progression if sooner, assessed in the evaluable population (all randomly assigned participants who had a scan at week 24 [or sooner if they progressed] with target marker lesions measured). Safety was assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01337401; the European Clinical Trials database, number EudraCT2010-021163-33; and the ISRCTN registry, number ISRCTN63733470 recruitment is complete and follow-up is ongoing. Findings: Between July 15, 2011, and July 29, 2016, of 48 participants recruited, all were randomly assigned to cediranib (n=32) or placebo (n=16). 23 (48%) were female and the median age was 31 years (IQR 27–45). Median follow-up was 34·3 months (IQR 23·7–55·6) at the time of data cutoff for these analyses (April 11, 2018). Four participants in the cediranib group were not evaluable for the primary endpoint (one did not start treatment, and three did not have their scan at 24 weeks). Median percentage change in sum of target marker lesion diameters for the evaluable population was −8·3% (IQR −26·5 to 5·9) with cediranib versus 13·4% (IQR 1·1 to 21·3) with placebo (one-sided p=0·0010). The most common grade 3 adverse events on (blinded) cediranib were hypertension (six [19%] of 31) and diarrhoea (two [6%]). 15 serious adverse reactions in 12 patients were reported; 12 of these reactions occurred on open-label cediranib, and the most common symptoms were dehydration (n=2), vomiting (n=2), and proteinuria (n=2). One probable treatment-related death (intracranial haemorrhage) occurred 41 days after starting open-label cediranib in a patient who was assigned to placebo in the masked phase. Interpretation: Given the high incidence of metastatic disease and poor long-term prognosis of ASPS, together with the lack of efficacy of conventional chemotherapy, our finding of significant clinical activity with cediranib in this disease is an important step towards the goal of long-term disease control for these young patients. Future clinical trials in ASPS are also likely to involve immune checkpoint inhibitors. Funding: Cancer Research UK and AstraZeneca.

Background Nitrogen containing bisphosphonates such as zoledronic acid (ZA) are known to contain certain anti-cancer properties. These have been investigated in the past in various cancers such as breast, prostate and colon. ZA in particular has shown promising results in pre-clinical studies. We propose a multicentre double-blind randomised controlled feasibility study to assess the recruitment and acceptability of ZA/placebo alongside chemotherapy in malignant pleural mesothelioma (MPM). Methods Patients will be recruited for a 13-month period from October 2016 to November 2017. Eligible patients will be identified via the regional mesothelioma multidisciplinary team meeting. Those who receive chemotherapy will be randomised to receive either ZA or placebo alongside their chemotherapy. Those who decline chemotherapy will be offered to join the trial on the non-randomised open-labelled arm of the trial. Patients will receive a maximum of six cycles of ZA/placebo, at three-weekly cycles. All patients will be followed up for six months from randomisation. Semi-structured interviews to gather data on acceptability of trial procedures, tolerability of ZA and other relevant information will take place after the participants have completed their six cycles of treatment. For a better understanding about non-participation in mesothelioma trials we also aim to interview those who decline to take part in the trial. Discussion The qualitative and quantitative data gathered in this feasibility trial will hopefully pave the way to designing a robust full phase III trial to investigate the potential synergistic effect of ZA and current standard treatment for MPM, cisplatin-pemetrexed combination chemotherapy. Trial registration ISRCTN Registry, ISRCTN45536692. Registered on 9 August 2016. EudraCT no. 2015–004433-26. Electronic supplementary material The online version of this article (10.1186/s13063-018-2851-9) contains supplementary material, which is available to authorized users.

Background: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. Method: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. Results: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. Conclusions: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

Background Soft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues. Gastrointestinal stromal tumour (GIST) is the commonest STS and arises within the wall of the gastrointestinal (GI) tract. While most GISTs occur in the stomach they do occur in all parts of the GI tract. As with other STS, it is important that GISTs are managed by expert teams, to ensure consistent and optimal treatment, as well as recruitment to clinical trials, and the ongoing accumulation of further knowledge of the disease. The development of appropriate guidance, by an experienced panel referring to the evidence available, is therefore a useful foundation on which to build progress in the field. Methodology British Sarcoma Group guidelines for the management of GIST were initially developed by a panel of physicians experienced in the management of GIST. This current version has been updated and amended with reference to other European and US guidance. We have received input from representatives of all diagnostic and treatment disciplines as well as patient representatives. Levels of evidence and strength of recommendation gradings are those used by ESMO adapted from those published by the Infectious Disease Society of America. Conclusions The guidelines cover aetiology, genetics and underlying molecular mechanisms, diagnosis and initial investigations, staging and risk stratification, surgery, neoadjuvant and adjuvant therapy, the management of advanced disease and follow-up. The importance of mutational analysis in guiding treatment is highlighted, since this can indicate the most effective treatment and avoid administration of ineffective drugs, emphasising the need for management in specialist centres.

As UK health professionals specialising in the drug treatment of cancer, we think that Wise’s analysis strays into the territory of unbalanced opinion.1 We welcome discussion of topics that we debate ourselves; his article is a useful counterpoint to the hyperbole we often see in the media around incremental improvements in treatment. But he conflates problems from different …

In the Association of Cancer Physicians’ (ACP’s) new strategy for medical oncology in the United Kingdom, we are taking a broad view of developments which will bring benefits to patients with cancer and identifying the contributions that we can make to achieving these goals. Our consultants and their teams have contributed substantially to improvements in cancer outcomes over the past 25 years. We are greatly encouraged that over 50% of UK cancer patients now survive their disease for 10 years or more. We are at a time not only of unprecedented acceleration of knowledge with regard to all aspects of cancer, but also of rapid change in terms of patient management and new therapies. To deliver better outcomes for patients, we must overcome challenges over the next decade, such as increased demand for cancer services and financial constraint in the NHS.\ud \ud The first version of the ACP strategy was published on 13 July 2015. This second version is prepared as an update to reflect the publication of the Report of the Independent Cancer Taskforce entitled ‘Achieving World-Class Cancer Outcomes. A Strategy for England 2015–2020’ [1]. We have also responded in this strategy to helpful meetings with the President and the Senior Officers of the Royal College of Physicians. These inputs, arising soon after the initial publication of our strategy, were felt by the ACP Executive to be of sufficient importance to justify bringing forward the annual update of our strategic document.

BACKGROUND: Safety and cellular immunogenicity of rising doses and varying regimens of a poly-epitope vaccine were evaluated in advanced metastatic melanoma. The vaccine comprised plasmid DNA and recombinant modified vaccinia virus Ankara (MVA) both expressing a string (Mel3) of seven HLA.A2/A1 epitopes from five melanoma antigens. METHODS: Forty-one HLA-A2 positive patients with stage III/IV melanoma were enrolled. Patient groups received one or two doses of DNA.Mel3 followed by escalating doses of MVA.Mel3. Immunisations then continued eight weekly in the absence of disease progression. Epitope-specific CD8+ T cell responses were evaluated using ex-vivo tetramer and IFN-gamma ELISPOT assays. Safety and clinical responses were monitored. RESULTS: Prime-boost DNA/MVA induced Melan-A-specific CD8+ T cell responses in 22/31 (71%) patients detected by tetramer assay. ELISPOT detected a response to at least one epitope in 10/31 (32%) patients. T cell responder rates were

We have recently reported the results of a phase II trial in which two TroVax [modified vaccinia ankara (MVA) encoding the tumour antigen 5T4] vaccinations were given to patients both pre- and post-surgical resection of liver metastases secondary to colorectal cancer (CRC). 5T4-specific cellular responses were assessed at the entry and 2 weeks after each vaccination by proliferation of fresh lymphocytes and ELISA for antibody responses; 18 from the 19 CRC patients mounted a 5T4-specific cellular and/or humoral response. Here, we present a comparison of individual and between patient responses over the course of the treatments using cryopreserved peripheral blood mononuclear cells (PBMC) samples from the baseline until after the fourth vaccination at 14 weeks. Assays used were proliferation assay with 5T4-Fc fusion protein, overlapping 32mer 5T4 peptides, MVA-LacZ and MVA-5T4 infected autologous monocytes. Responses to 5T4 protein or one or more peptide pools were pre-existing in 12/20 patients and subsequently 10 and 12 patients showed boosted and/or de novo responses, respectively. Cumulatively, 13/20 patients showed proliferative responses by week 14. We also assessed the levels of systemic T regulatory cells, plasma cytokine levels, phenotype of tumour-infiltrating lymphocytes including T regulatory cells and tumour HLA class I loss of expression. More than half of the patients showed phenotypes consistent with relative immune suppression and/or escape highlighting the complexity of positive and negative factors challenging any simple correlation with clinical outcome.

Background: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. Methods: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil–lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. Findings: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR

The 5T4 oncofoetal antigen is a heavily glycosylated cell surface protein found on human placental trophoblast and on diverse types of human cancer but is not expressed at significant levels on adult human tissues in health. It therefore satisfies the criteria for a tumour-associated antigen and is an ideal target for the immunotherapy of cancer. We report here that 5T4 is strongly expressed on the majority of renal cell carcinomas and therefore this population of patients is suitable for trials of 5T4-targeted therapies. In particular, we have shown that T cells from renal cell carcinoma patients can be genetically modified to kill 5T4 expressing renal cancer cell lines by introduction of a chimeric-signalling protein. This protein consists of a single chain antibody fragment capable of binding antigen directly at the cell surface and then activating the T cell by virtue of a CD3zeta-signalling domain. This is a powerful tool that bypasses a number of mechanisms that allow tumours to escape T-cell killing and can be readily scaled up for clinical use.

11004 Background: ASPS is a rare disease (0.5-1% of soft tissue sarcomas) mainly affecting young people. It is unresponsive to conventional chemotherapy. Cediranib (C), an inhibitor of vascular endothelial growth factor receptors and other receptor tyrosine kinases, has shown significant activity in ASPS in single arm phase II trials. CASPS (NCT01337401) was designed to permit discrimination between the impact of cediranib and the often intrinsically indolent nature of the disease. Methods: CASPS compared C (30mg od) with placebo (P) in a 2:1 double blind randomisation in patients (pts) age ≥16 years with metastatic ASPS progressive in the previous 6 months. Pts were unblinded at week 24, or at progression if sooner, when those on P started C. The primary endpoint of percentage change in the sum of target marker lesions (TMLsum) between baseline and week 24 (or progression if sooner) was compared between groups by Mann-Whitney test. Secondary endpoints were progression-free survival (PFS), week 24 response rate and best response (RECIST v1.1), safety/tolerability and overall survival (OS). One-sided p-values and two-sided 90% confidence intervals are reported. Results: 48 pts were recruited between 07/2011 and 07/2016 from 12 centres (UK, Australia & Spain). 52% of pts were female, median age was 31. Most common grade ≥3 adverse events on C were hypertension (23%), diarrhoea (14%) and fatigue (9%). In the evaluable population (N = 44) median change in TMLsum on C was minus 8.3% (IQR minus 26.2% to +5.9%); versus P: +13.4% (IQR minus 0.6% to +21.3%), p = 0.0013. Best response by week 24 was partial response for 6/28 (21%) C pts compared with 0/16 on P (p = 0.053) and stable disease for an additional 19/28 (68%) on C and 12/16 (75%) on P. The PFS HR (C versus P) was 0.54 (90% CI 0.30-0.97, p = 0.041), median PFS: 10.8 mths on C versus 3.7 mths on P, OS at 12 mths was C: 96%; P: 64.3%. Conclusions: CASPS, the largest randomised trial to date in this disease, confirms the activity of C in ASPS, showing a significant reduction in tumour burden and improvement in PFS. Tumour tissue and serial blood samples will subsequently be investigated to identify potential predictive and prognostic biomarkers. Clinical trial information: NCT01337401.

Monthly intravenous pegylated liposomal doxorubicin (PLD) 50 mg m(-2), although well tolerated, showed almost no activity in this phase II study of 16 patients with advanced hepatocellular carcinoma with a response rate of 0%, stable disease 19%, median time to progression of 2.4 months, 1-year survival of 25% and median survival of 6.5 months.

We investigated the use of a therapeutic vaccine, TroVax in patients undergoing surgical resection of colorectal cancer liver metastases. Systemic immunity generated by vaccination before and after resection of metastases was measured in addition to assessing safety and analyzing the function and phenotype of tumor-associated lymphocytes. Twenty patients were scheduled to receive 2 TroVax vaccinations at 2-week intervals preoperatively and 2 postoperatively; if immune responses were detected, 2 further vaccinations were offered. Blood was taken at trial entry and 2 weeks after each vaccination; tumor biopsies were collected at surgery. 5T4-specific cellular responses were assessed by lymphocyte proliferation and enzyme-linked immunosorbent spot, with antibody responses by enzyme-linked immunosorbent assay. Immunohistochemistry characterized the phenotype of tumor-infiltrating lymphocytes. Seventeen of 19 colorectal cancer patients showed 5T4 expression in the liver metastases or surrounding stroma and 18 mounted a 5T4-specific cellular and/or humoral response. In patients who received at least 4 vaccinations and potentially curative surgery (n=15), those with above median 5T4-specific proliferative responses or T-cell infiltration into the resected tumor showed significantly longer survival compared with those with below median responses. Seven of 8 patients who had preexisting proliferative responses to 5T4 were longer-term survivors; these patients showed significantly higher proliferative responses after vaccination than those who subsequently died. These data suggest that the magnitude of 5T4 proliferative responses and the density of CD3 cells in colorectal cancer liver metastases are associated with longer survival. These observations warrant more studies to identify the precise underlying mechanisms.

Ascites is the abnormal accumulation of fluid in the peritoneal cavity. Men have little or no peritoneal fluid, but women may have up to 20 ml depending on the phase of the menstrual cycle. Ascites is a relatively common clinical finding with a range of malignant and non-malignant causes (Table 1). About 85% of ascites is caused by liver disease (Runyon, 2004), and cancer accounts for about 10% of cases (Smith and Jayson, 2003; Becker et al, 2006).

Using the immune system to treat cancer is an attractive proposition for patients and their doctors. It suggests low toxicity therapy, manipulating a natural process, to prevent or cure disease. Exciting advances in cancer vaccine development have recently been made.

2574 Background: Oncofetal antigen 5T4 is expressed by most colorectal cancers. Administration of a vaccine combining a Modified Vaccinia Ankara (MVA) vector with 5T4 elicits immune responses in late-stage colorectal cancer patients. This trial seeks to investigate the immunological effects of the vaccine both in peripheral blood and locally in tumour tissue resected during potentially curative surgery for colorectal liver metastases. Some patients may have micrometastatic disease, a potential target for immunotherapy. Methods: Colorectal cancer patients selected for resection of liver metastases were eligible. Recruitment of up to 20 patients was planned. Following screening they received 2 vaccinations prior to, and 2 after, surgery. Primary endpoint was assessment of the immune response at time of surgery. Blood was taken for analysis at screening and 2 weeks after each vaccination. A tumour biopsy was obtained at surgery. T-cell responses were assessed using proliferation and gamma-interferon ELISPOT assays; ELISA used to assess serological response. Immunohistochemical analysis was used to confirm tumour antigen expression and the nature of T-cell infiltration into the liver. If 5T4-specific immune responses were demonstrated patients were offered further vaccinations at 20 and 28 weeks post surgery. Results: Of 20 patients recruited, 16 were eligible for assessment, 4 excluded, 1 due to hepatocellular carcinoma, 3 with inoperable disease. There was no grade III/IV toxicity related to vaccination. Tumour expression of 5T4 was confirmed in all cases, local T-cell infiltration consisted predominantly of CD4 cells. According to proliferation assays, 8 of 16 patients had T-cell responses at time of surgery and 12 of 16 in total to date. 14 patients have developed 5T4-specific antibody responses. At median follow up of 8.4 months 7 of 16 patients have disease recurrence. Conclusions: The MVA-5T4 vaccine (TroVax) was safe and well tolerated in all patients undergoing resection of colorectal liver metastases. 5T4 specific cellular and/or humoral immune responses were induced in the majority of patients following vaccination with TroVax. [Table: see text]

2570 Background: This study evaluates the safety, immunogenicity and clinical response (by RECIST criteria) of increasing doses of DNA plasmid (DNA.Mel3) and MVA viral vector (MVA.Mel3) containing ...

8030 Background: This trialevaluated the safety, immunogenicity and tumour response of increasing doses of DNA plasmid (DNA.Mel3) and MVA viral vector (MVA.Mel3), containing 7 melanoma epitopes. Methods: 41 HLA-A2 positive stage III/IV melanoma patients with unresectable measurable disease were enrolled. Immunisations were administered three weeks apart with continued MVA.Mel3 boosting in patients with tumour control. Epitope-specific CD8+ T cell responses were evaluated using ex vivo tetramer staining and interferon gamma (IFN-γ) ELISPOT assay. Results: DNA.Mel3 was well tolerated at all doses. Dose-related grade 3 local skin reactions and systemic immune-associated reactions were observed following MVA.Mel3, no reactions led to early study discontinuation. Melan-A tetramer responses were observed in 23/36 (64%) evaluable patients, of which 9/36 showed an IFNγ response to at least one epitope in ELISPOT assay. Seven patients (17%) showed tumour control (PR, MR, or SD >6 months), of which 3/7 patients had associated immune responses, including one with PR > 21 months who underwent extended MVA.Mel3 boosting. Overall median progression free survival was 9 weeks (16 weeks for immune responders). Median overall survival for the intention-to-treat population is 11.7 months with follow up of 16 patients continuing. Conclusions: High dose heterologous PrimeBoost immunisation was safe and stimulated immune responses in >50% of late stage metastatic melanoma patients treated. Tumour control was observed with some evidence of association with immune response. [Table: see text] [Table: see text]