Tumour genotype plays an important role in drug resistance in patients with metastatic colorectal cancer, however, the genotype obtained at diagnosis can vary after different treatment lines. Therefore, DNA analysis using liquid biopsy has clear advantages over DNA analysis with tissue biopsy and is rapidly gaining importance and momentum in the oncology field.
An international large-scale study from researchers at the Vall d’Hebron Institute of Oncology analyzed the DNA of 503 patients with metastatic colorectal cancer by liquid biopsy (BEAMing platform) to detect KRAS, PIK3CA and BRAF gene mutations in tumours. These patients, who had previously received different treatment lines, were administered either the multi-kinase inhibitor regorafenib or placebo. Regorafenib is an inhibitor of several proteins involved in oncogenesis and tumour angiogenesis.
Previous studies show that liquid biopsy, also known as a blood-based biomarker test, is a fast, simple method for detecting RAS (KRAS and NAS) mutation status in tumours, as it only requires a blood test rather than a tissue biopsy or surgical procedure. Further, it also provides mutation status results in a matter of days, helping to determine the most specific, targeted treatment in each case. It represents one more important step in realizing the true promise of precision medicine in oncology, the main focus behind research by the team which aims to both advance and deliver targeted therapies tailored to the particularities of each tumour for an increasing number of patients.
The current study is the first large-scale clinical trial to compare liquid versus conventional tissue biopsy data, and the results show the former (BEAMing technology) obtain more data on tumour mutation throughout the course of the disease, enabling the team to better target therapy to the specificities of patient´s tumour. The team state that this could have a considerable impact on clinical practice, as novel applications of this technology could be further investigated and developed
The majority of earlier clinical studies published on the use of DNA in blood to determine tumour genotype, have only enrolled a relatively small number of patients which limits the significance of the findings as well as the ability to research possible correlations between genotype and clinical outcome. Furthermore, most studies evaluated a single gene (such as KRAS) and used technologies that are not commercially available. The researchers explain that the importance of the current CORRECT trial is that it involved a large number of patients, providing correlative analyses that showed clinical benefits of regorafenib in all the subgroups in which mutations had been identified.
The results show that liquid biopsy effectively unmasked different tumour-related mutations. More specifically, in a subgroup of 41 patients who had previously received anti-EGFR therapy, it was revealed that they had acquired KRAS mutations during the course of their disease. The lab state that such accurate information is difficult to obtain using tissue biopsy which could, in the absence of this data, lead to a selection of therapy which may not be the most appropriate for these patients. Moreover, the data findings show that regorafenib is effective in patients with KRAS and PIK3CA mutations.
The researchers surmise that although there are still some important questions that will need to be resolved concerning liquid biopsy, for example, the possibility that not all tumours release enough DNA into the blood for it to be detected, as well as the difficulty of assigning a particular genotype for each particular tumour in patients with multiple metastases, the CORRECT study shows that liquid biopsy could become an essential tool in clinical practice.