Spanish researchers claim expression levels of the cancer-associated gene AEG-1 (astrocyte elevated gene 1, or metadherin) correlate closely with how well non-small cell lung cancer (NSCLC) patients receiving erlotinib will respond to their treatment. They hope their findings could lead to the development of a prognostic assay, possibly in combination with BRCA1 expression, to predict those patients who will derive the maximum benefit from EGFR-tyrosine kinase inhibitors. The researchers are part of the Spanish Lung Cancer Group (SLCG), which worked in cooperation with Pangaea Biotech and USP Dexeus University Institute in Barcelona, which acts as one of the reference laboratories for the SLCG. They report their findings at the European Multidisciplinary Conference in Thoracic Oncology, taking place in Lugano, Switzerland.
“Currently we have no predictors for the duration of response to EGFR drugs in NSCLC patients with EGFR mutation,” explains Rafael Rosell, Ph.D., lead researcher. “The median progresson-free survival (PFS) time for these patients ranges from 10-14 months, but there is a subgroup of patients with very short response while others have long-lasting benefit.”
In order to try and identify genes predictive of response to erlotinib, the Spanish team used NanoString technology to detect the expression levels of 48 genes in 43 patients with EGFR-mutated NSCLC cancer receiving erlotinib. The results suggested that AEG-1 expression was the strongest predictor of PFS time. Patients with low AEG-1 expression demonstrated a PFS of 27 months, while PFS was just 12 months in patients with high AEG-1 expression.
The potential use of an assay evaluating AEG-1 expression in combination with BRCA1 gene expression could be of major clinical benefit when used alongside radiographic monitoring and could provide an indication of treatment response, Dr. Rosell suggests. “Defining a low-risk subgroup of patients can accurately predict situations when the simple administration of an oral EGFR drug could have an extremely durable effect, of more than two years.” Conversely, he adds, a high-risk result could alert the clinical oncologist that the patient may be likely to demonstrate early progression, and so look for an alternative management strategy.