26/02/2015
Barcelona February 26, 2014 - Researchers from the Spanish Lung Cancer Group (SLCG) and the Dr Rosell Oncology Institute published today in the prestigious journal JAMA Oncology their article “Association of EGFR L858R mutation in circulating free DNA with survival in the EURTAC trial” in which they demonstrate the feasibility of using circulating free DNA (cfDNA) from blood samples collected from advanced non-small cell lung (NSCLC) patients as a substitute for cancer tissue biopsies.
“Testing of tumor tissue remains the recommended method for detecting the presence of oncogenic EGFR mutations; however, the amount of tumor tissue obtained by biopsy is often insufficient, especially in advanced NSCLC, raising the question of whether cfDNA may be used as a surrogate liquid biopsy for the noninvasive assessment of EGFR mutations,” the study notes.
Using this innovative technique, the group led by Dr Rafael Rosell sought to detect mutations in the epidermal growth factor receptor (EGFR) gene that drive tumor growth, and correlate the presence of such mutations with survival times for these patients.
The analysis was a secondary objective of the EURTAC trial, sponsored by the Spanish Lung Cancer Group (GECP), which led to approval of the Roche inhibitor Tarceva® by the FDA in 2013 for first-line treatment of patients with EGFR mutations. To perform this analysis, Dr Rosell and coauthors examined EGFR mutations in cfDNA isolated from 97 blood samples. In 76 of 97 samples (78%) of patients, mutations in EGFR were detected in cfDNA.
Median overall survival was shorter in patients with the EGFR L858R mutation in cfDNA than in those with exon 19 deletion (13.7 vs. 30 months). For patients with the L858R mutation in tissue, average overall survival was 13.7 months for patients with the L858R mutation in cfDNA and 27.7 months for those in whom the mutation was not detected in cfDNA. For the 76 patients with EGFR mutations in cfDNA, only treatment with Tarceva® was an independent predictor of disease and progression-free survival. Therefore, the presence of the EGFR L858R mutation and its detection in blood can now be considered a prognostic and predictive factor with applications for clinical practice. The trial is the first to compare survival in advanced NSCLC according to detection of mutations in cfDNA vs. tissue.
The EURTAC is not the first trial to incorporate genetic testing in blood. However, the test developed by researchers at the Pangaea Biotech laboratory and recently licensed by Labco Quality Diagnostics is the first to have the required sensitivity and specificity for incorporation into daily clinical practice.
According to Dr. Rosell "There have been great advances in the treatment of lung cancer in recent years, but many questions still remain. To start looking for the answers, we need new trials that incorporate testing in blood. For example, something which is becoming increasingly clear is that treatment with single drugs against mutated EGFR is insufficient. With this in mind, we are currently conducting two large-scale clinical trials, the BELIEF and GOAL, with combinations of drugs, in which we are using the Pangaea Biotech test to analyze EGFR mutations in serum before starting therapy, again at time of response and again at time of progression. These trials could help to improve treatment and could be the first monitor EGFR mutations in cfDNA".
Dr Rosell believes "The need to identify EGFR mutations in cfDNA, and to continuously monitor response to treatment during the course of the disease is clear. Thanks to JAMA Oncology, I hope this need will become more widely accepted. In addition, thanks to our partners Labco Quality Diagnostics we now have the ability to reach even more patients with the distribution of our blood detection test via the largest network of clinical laboratories in Europe and Latin America.
Treatment of NSCLC has changed dramatically since it was discovered in 2004 that mutations in the EGFR gene cause lung cancer in some patients (especially those with lung adenocarcinomas, women, nonsmokers or former smokers). Screening for EGFR mutations can now determine which patients are most likely to benefit from targeted drugs such as Tarceva®; patients treated with this drug have significantly better and longer lasting responses compared with standard chemotherapy. As previously mentioned, due to the difficulties involved in obtaining tumor tissue by traditional biopsy, this new blood detection technique is a promising method for EGFR mutation screening.
The Spanish Lung Cancer Group (SLCG) and the EURTAC trial
The Spanish Lung Cancer Group was founded by a group of medical oncologists in 1991 with a clear objective: to advance the treatment of lung cancer through research and prevention. The SLCG is a multicenter, multidisciplinary cooperative group incorporating more than 132 hospitals and 260 Spanish doctors specialized in medical oncology, thoracic surgery and basic research. It carries out clinical research activity in different types of lung cancer and different clinical situations, from initial to advanced stages, and has treated some 8,000 patients in more than 60 protocols and clinical trials. The SLCG also participates, develops and coordinates international cooperative projects with other lung cancer clinical research groups.
The EURTAC trial, sponsored by the SLCG, was the first to demonstrate the superiority of Tarceva® over chemotherapy in patients with mutant EGFR. The trial results were key for the approval of Tarceva by the European Medical Agency (EMA) and the US Food and Drug Administration (FDA) for first-line treatment of these patients.
