MAGE-A3 expression in patients screened for the DERMA trial: A phase III trial testing MAGE-A3 immunotherapeutic in the adjuvant setting for stage IIIB-C-Tx melanoma.

Abstract

8559 Background: Administration of MAGE-A3 immunotherapeutic involves the active immunization of patients (pts) with tumors expressing the MAGE-A3 protein. This new investigational approach has been previously assessed in two phase II trials, one in pts with metastatic melanoma (NCT00086866) and another in pts with completely resected non-small cell lung cancer (NCT00290355). Based on the positive responses observed in both studies, a randomized phase III placebo controlled trial assessing MAGE-A3 immunotherapeutic as adjuvant treatment in pts with resected, regionally advanced melanoma (stage IIIB-C-Tx AJCC/UICC 2010) is currently ongoing (DERMA Phase III trial, NCT00796445). Methods: Formalin-fixed, paraffin-embedded tumor tissues were prepared from surgically removed metastatic lymph nodes and tested for MAGE-A3 expression by qRT-PCR. Other baseline patient and tumor characteristics were collected during screening to further investigate factors that could potentially influence MAGE-A3 expression. Results: Between Dec 1, 2008 and Oct 25, 2011, 3917 pts were screened. Of the 3,183 valid samples (excluding the 513 inconclusive tests [66% for poor quality, 27% out-of range, 7% miscellaneous]) and the 221 missing samples, 2,092 (65.7%) were positive for MAGE-A3 expression. In these stage III melanoma pts, no difference in MAGE-A3 expression levels were identified with regard to (1) disease stage - IIIB (62.6%), IIIC (66.5%) and IIITx (66.2%); (2) gender - male (64.2%), female (68.1%); (3) age group - 18 to 39 years (63.2%), 40 to 49 years (65.3%), 50 to 59 years (66.8%), 60 to 69 years (68.1%) and 70 years and over (63.4%) and (4) region: Europe (66.1%), North America (63.0%) and rest of the world including Argentina, Brazil, Australia, Mexico, Taiwan, Japan, Korea (67.9%). Conclusions: Expression of the MAGE-A3 gene in the DERMA trial population (stage IIIB-IIIC-IIITx) was 66%. It was not correlated with age, gender, disease stage or geographic region. This expression frequency is consistent with published data in metastatic melanoma (Van den Eynde, 1997; Vourc’h-Jourdain et al, 2009) and has potentially important clinical implications.