‘Liquid biopsy’ able to detect early resistance to targeted therapy in advanced lung cancer patients

Published: 2015-06-24
  • Monitoring of EML4-ALK gene rearrangements in blood platelets is sufficiently sensitive and specific to be incorporated into clinical practice.
  • Non-invasive blood samples can be taken repeatedly, overcoming the challenges associated with obtaining sufficient tumor tissue for genetic analyses.
  • The ability to detect disease progression in ‘real time’ allows oncologists to predict treatment outcomes, switch therapies when necessary and increase life expectancy.

Barcelona, June 3 2015 - Investigators from Pangaea Biotech, Barcelona, and thromboDx, Amsterdam, have demonstrated how a rearrangement in the EML4-ALK genes which drives tumor growth can be detected in blood samples from advanced non-small-cell lung cancer (NSCLC) patients. By monitoring EML4-ALK in blood platelets, researcherswere able to detect drug resistance and predict outcomes to targeted therapy with the ALK inhibitor Xalkori®. Results of the study EML4-ALK rearrangement in blood platelets and outcometo crizotinib in non-small-cell lung cancer patients were presented at the annual congress of the AmericanSociety of Clinical Oncology(ASCO) in Chicago in May.

To perform the analyses, the investigators analyzed EML4-ALK rearrangements in platelets and plasma from blood of 77 NSCLC patients, 38 of whom had EML4-ALK-rearranged tumors. In a further subset of 29 patients treated with Xalkori®, detection of EML4-ALK in platelets was correlated with progression-free survival and overall survival. It emerged that, among these 29 patients, those positive for the rearrangement in platelets experienced disease progression after just 3.7 months, while this was much longer - 16 months - for those without the rearrangement. The innovative blood-based assay was able to detect EML4-ALK in 65% of patients with 100% specificity, making it an accurate and reliable tool for predicting outcome to crizotinib.

Even more exciting was the discovery that monitoring EML4-ALK rearrangements in platelets from one patient over a period of 30 months revealed crizotinib resistance two months prior to disease progression detected by radiographic imaging. This kind of valuable information can complement conventional techniques and allow doctors take more informed treatment decisions sooner, tailor therapy to each patient and thereby increase life expectancy.

Dr Rafael Rosell, leader of the Pangaea Biotech team states “It is becoming increasingly clear that we need to find alternatives to traditional tumor tissue biopsies to perform vital genetic analyses. For example, in the case of advanced lung cancer, some 25% of patients have insufficient biopsied tissue. Also, taking a tissue biopsy is an invasive process; it is difficult to ask patients to submit to it repeatedly. Therefore there is an urgent need for reliable assays to perform serial analyses of tumoral genetic material in alternative biosources such as blood and monitor treatment response in real time.”

Dr Rosell’s group is at the forefront of the search for alternative biosources; in February they jointly published the articleAssociation of EGFR L858R mutation in circulating free DNA with survival in the EURTAC trial in JAMAOncology with researchers from the Spanish Lung Cancer Group. The study demonstrated the feasibility of using free circulating DNA (cfDNA) from blood samples collected from advanced NSCLC patients a substitute for tissue biopsies. The test used – now available to patients thanks to Pangaea Biotech’s strategic alliance with LABCO Quality Diagnostics – was the first to be sufficiently sensitive (78%) and specific (100%) to be incorporated into daily clinical practice.

About Dr Rafael Rosell

The Pangaea Biotech team is led by Dr Rafael Rosell, MD,PhD, founder of the Spanish Lung Cancer Group, President and Scientific Director of Pangaea, and Director of the Cancer Biology and Precision Medicine Program at the Catalan Institute of Oncology (ICO). Dr. Rosell’s contributions to translational medical oncology, with particular emphasis on the field of non-small-cell lung cancer with EGFR mutations, have earned him international recognition: in 2013 he was recognized by The Lancet as the highest authority in lung cancer in Europe, and he has received numerous awards in recognition of his tireless investigations into the causes and treatment of cancer.

About Pangaea Biotech

Pangaea Biotech, founded in 2007, is a biotechnology company focused on development of drugs and new diagnostic tools. The company has three main areas of activity: patient care via the Dr Rosell Oncology Institute (IOR) in the Quiron Dexeus University Hospital, development of diagnostic tools and services, and development of new anti-cancer drugs.

About thromboDx

thromboDx is a molecular diagnostics company founded in 2011 that develops and commercializes blood-based diagnostics through its proprietary platelet-based technology platform. thromboDx addresses the need for an easily accessible, minimally invasive biomarker source for detection and monitoring of cancer using their thromboPCR and thromboSeq platforms. The platelet-based technology platform was developed by the group of Dr Thomas Wurdinger, PhD (Cancer Center Amsterdam). thromboDx is based in Amsterdam, the Netherlands, and works closely with doctors to develop and validate new blood tests to monitor therapy responses,including the newest thromboPCR test to monitor EML4-ALK levels and thromboSeq tests to detect early-stage cancer and to monitor alterations in KRAS, EGFR, PIK3CA, BRAF, HER2, MET, and ALK.