A new study presented at the ESMO Congress 2019 shows that a sophisticated blood test to pick up circulating tumor DNA could soon help avoid having to take a tissue biopsy in some patients with lung cancer. A tissue biopsy is typically required to decide on appropriate treatment. Instead, the findings of the BFAST trial focused on the usefulness of ‘liquid biopsy’ in this situation. This means drawing a blood sample to look for traces of tumor DNA shed from tumor cells into the bloodstream and analyzing them to understand the tumor characteristics.

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The phase II/III BFAST Trial was aimed at taking advantage of new genomic technologies that allow small amounts of DNA to be detected, amplified and analyzed at high speeds and low cost. Thus, next-generation DNA sequencing methods were used to detect ‘driver mutations’. These are complex changes in the tumor cell DNA that stimulate the progression of the tumor from early to advanced stages. These predict the behavior of the tumor and its response to treatment with specific or targeted therapy with molecules that act against a specific protein. While these mutations can be targeted by specific drugs, it is difficult to obtain a sample of the tumor that allows such an analysis. The usefulness of the current trial that blood samples to derive DNA for analysis is, therefore, plain to see.

What happened during the study?

The BFAST trial included over 2,200 patients with non-small cell lung cancer (NSCLC) and without a history of prior treatment. NSCLC is the most common type of lung cancer, accounting for about 85% of all cases. They resist traditional chemotherapy and carry a poor prognosis.

The patients were given blood tests for circulating tumor DNA, in particular, the ALK mutation, which is a complex driver mutation. The presence of this mutation causes the protein to function autonomously, causing tumor formation. It is present in about 12% of younger patients with a history of not smoking or only light smoking, but only 2% of those who currently smoke.

Almost 2,200 patients returned positive results for circulating tumor DNA, and the ALK mutation proved to be present in about 5% of patients (almost 120 patients). According to cancer specialists, this mutation is difficult to detect, so the fact that it can be picked up by a blood test is encouraging.

Moreover, the ALK is very sensitive to treatment with the monoclonal antibody alectinib (though the rapid development of resistance is also common). In the current trial, 87 patients were treated with this drug and followed up for over a year. Following such treatment, the study showed that more than 78% of patients had a stable disease – no signs of disease progression – for the next 12 months. The objective response rate (ORR) was over 87%. This means that this percentage of patients showed a reduction in tumor size according to a preset criterion which lasted for a predefined time as well. The effect of the treatment lasted for at least 12 months in 75% of patients. The adverse effects were no more than expected with this drug.

Liquid biopsy identified a similar proportion of patients with ALK mutations to that typically seen with traditional biopsy, and the results with alectinib compared well with those seen in a pivotal study of this treatment.” Researcher Shirish Gadgeel

The coupling of these two findings – the comparable sensitivity of detection of ALK mutations by liquid biopsy, with the effectiveness of ALK inhibitor therapy – is “an important advance”, according to oncologist Alberto Bardelli.

It is encouraging to see that increasing numbers of patients with lung cancer can benefit from liquid biopsy to identify their disease mutation instead of tissue samples. At present the technology is quite expensive but as it becomes more widely used, the cost is likely to come down so that testing becomes more affordable and available in daily practice.” Shirish Gadgeel