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Despite newly approved treatments, metastatic melanoma remains a life-threatening condition. We aimed to evaluate the efficacy of the MAGE-A3 immunotherapeutic in patients with stage IIIB or IIIC melanoma in the adjuvant setting. DERMA was a phase 3, double-blind, randomised, placebo-controlled trial done in 31 countries and 263 centres. Eligible patients were 18 years or older and had histologically proven, completely resected, stage IIIB or IIIC, MAGE-A3-positive cutaneous melanoma with macroscopic lymph node involvement and an Eastern Cooperative Oncology Group performance score of 0 or 1. Randomisation and treatment allocation at the investigator sites were done centrally via the internet. We randomly assigned patients (2:1) to receive up to 13 intramuscular injections of recombinant MAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic; 300 μg MAGE-A3 antigen plus 420 μg CpG 7909 reconstituted in AS01B to a total volume of 0·5 mL), or placebo, over a 27-month period: five doses at 3-weekly intervals, followed by eight doses at 12-weekly intervals. The co-primary outcomes were disease-free survival in the overall population and in patients with a potentially predictive gene signature (GS-positive) identified previously and validated here via an adaptive signature design. The final analyses included all patients who had received at least one dose of study treatment; analyses for efficacy were in the as-randomised population and for safety were in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT00796445. Between Dec 1, 2008, and Sept 19, 2011, 3914 patients were screened, 1391 randomly assigned, and 1345 started treatment (n=895 for MAGE-A3 and n=450 for placebo). At final analysis (data cutoff May 23, 2013), median follow-up was 28·0 months [IQR 23·3–35·5] in the MAGE-A3 group and 28·1 months [23·7–36·9] in the placebo group. Median disease-free survival was 11·0 months (95% CI 10·0–11·9) in the MAGE-A3 group and 11·2 months (8·6–14·1) in the placebo group (hazard ratio [HR] 1·01, 0·88–1·17, p=0·86). In the GS-positive population, median disease-free survival was 9·9 months (95% CI 5·7–17·6) in the MAGE-A3 group and 11·6 months (5·6–22·3) in the placebo group (HR 1·11, 0·83–1·49, p=0·48). Within the first 31 days of treatment, adverse events of grade 3 or worse were reported by 126 (14%) of 894 patients in the MAGE-A3 group and 56 (12%) of 450 patients in the placebo group, treatment-related adverse events of grade 3 or worse by 36 (4%) patients given MAGE-A3 vs six (1%) patients given placebo, and at least one serious adverse event by 14% of patients in both groups (129 patients given MAGE-A3 and 64 patients given placebo). The most common adverse events of grade 3 or worse were neoplasms (33 [4%] patients in the MAGE-A3 group vs 17 [4%] patients in the placebo group), general disorders and administration site conditions (25 [3%] for MAGE-A3 vs four [<1%] for placebo) and infections and infestations (17 [2%] for MAGE-A3 vs seven [2%] for placebo). No deaths were related to treatment. An antigen-specific immunotherapeutic alone was not efficacious in this clinical setting. Based on these findings, development of the MAGE-A3 immunotherapeutic for use in melanoma has been stopped. GlaxoSmithKline Biologicals SA.

Background: Identification of lymph node metastasis is one of the most important indicators of poor prognosis in patients with colorectal carcinoma. Immunohistochemical techniques have improved possibilities of detection of micrometastases or even of isolated tumour cells in lymph nodes. Aim of study: The aim of this study was to determinate whether cytokeratin 20 (CK20), cytokeratin AE1/AE3 (CK AE1/AE3), epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) are markers of equal sensitivity to detect micrometastases in lymph nodes of colorectal carcinoma. Material and methods: Immunohistochemical analysis was made on all 570 formalin-fixed, paraffin-embedded lymph nodes and tumours from 50 consecutive patients (at the age from 44 to 69) with colon or rectum carcinoma. They had undergone radical resection in the Centre of Oncology in Bydgoszcz in 2003-2006. In no patients were lymph node metastases detected by routine haematoxylin-eosin staining. Immunohistochemical examination was done by EnVision method using monoclonal antibodies CK AE1/AE3, CK 20, EMA and CEA produced by Dako. Results: Immunohistochemical method detected micrometastatic disease in three lymph nodes from two patients. Noticeable micrometastases were found in sections from only one depth of lymph nodes. All micrometastatic tumour cells showed positive staining with antibody CK AE1/AE3 and negative with CK 20, EMA and CEA. Conclusions: From among immunohistochemical markers the most sensitive for micrometastases detection was anti-cytokeratin antibody CK AE1/AE3. Identification of lymph node micrometastases in sections from only one depth indicates them to be a serial cut.