Barcelona 14 March 2014 - Expert investigators from the Dr Rosell Oncology Institute this week published in Clinical Cancer Research their paper “The impact of EGFR T790M mutations and BIM mRNA expression on outcome in patients with EGFR-mutant NSCLC treated with erlotinib or chemotherapy in the randomized phase III EURTAC trial” describing two new biomarkers which can predict how well certain non-small-cell lung cancer (NSCLC) patients will respond to the anti-cancer therapy.



Treatment of NSCLC has changed dramatically since the discovery in 2004 that mutations in the epidermal growth factor receptor (EGFR) gene drive the disease in certain patients (mainly those with lung adenocarcinomas, women, and former- or never-smokers). Screening for EGFR mutations can now determine which patients are most likely to benefit from targeted drugs such as Tarceva® or Iressa®; lung cancer patients taking these drugs have significantly improved, longer-lasting responses when compared to chemotherapy. However, most eventually develop drug resistance and disease progression. Therefore, despite the potential for biomarker-directed therapy to extend response and survival times, in clinical practice the existence of multiple resistance mechanisms complicates selection of optimal biomarkers and limits use of these targeted therapies. Therefore, the challenge now for scientists now is to identify causes of resistance and propose solutions.



The group, led by Dr Rafael Rosell, wanted to find out why some patients who initially respond well to the drug Tarceva® go on to develop resistance. To do this, they analyzed causes of resistance in 95 EGFR-mutated NSCLC patients included in the EURTAC trial. They detected the EGFR T790M mutation at high frequency, 65%, even before any treatment had been administered, with a clear impact on progression-free survival. Patients treated with Tarceva who had the mutation lasted on average just 9.7 months before the disease progressed. By contrast, those without the mutation had 15.8 months free of progression. The negative effect of the mutation was not limited to Tarceva: chemotherapy-treated T790M-mutated patients lasted 6 months before developing disease progression; for those without the mutation this was 5.1 months. In these same 95 patients, high levels of activity of the BIM gene were also seen to be a marker of longer progression-free and overall survival (28.6 months vs 22.1 months for low/intermediate BIM expression).



The group is the first to determine the importance of these two markers in lung tumors with EGFR mutations. According to Dr Rosell “Combining assessment of T790M mutations and BIM with EGFR screening could represent a turning point in genetic assessment of these patients. If T790M is identified pre-treatment, when initial therapies fail, these patients can be offered alternative treatments designed to overcome resistance. Therefore, determining the causes of resistance can encourage more widespread use of biomarkers to select patients for targeted treatments”.



About the EURTAC trial



The EURTAC trial was the first to demonstrate the superiority of Tarceva over chemotherapy in Western EGFR-mutated patients. The results of the trial led to approval of Tarceva for first line treatment of these patients by both the European Medical Agency (EMA) and the US FDA.



About Dr Rafael Rosell



Dr Rafael Rosell is world-renowned for his contributions to translational oncology, in particular in the field of non-small-cell lung cancer. He is Head of the Dr Rosell Oncology Institute, Quirón Dexeus University Hospital, Barcelona; Head of the Medical Oncology Service, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona (Barcelona), President and Founder of the Molecular Oncology Research Foundation (MORe), President and Chief Scientific Officer of Pangaea Biotech S.L; Chairman and Founder of the Spanish Lung Cancer Group; Member, Foundation Council, European Thoracic Oncology Platform (ETOP).