Liquid biopsies, which are blood tests that measure circulating tumor DNA, could potentially be used as an early marker for immunotherapy response, according to a phase 2 clinical trial conducted in the US and Canada. The trial, led by researchers from various institutions including the Johns Hopkins Kimmel Cancer Center, BC Cancer, and the Canadian Cancer trials Group, aimed to determine the role of circulating tumor DNA (ctDNA) in monitoring immunotherapy response in patients with advanced non-small cell lung cancer.
Immunotherapies have shown promise in treating cancer, as they harness the power of the immune system to target cancer cells. However, the effectiveness of these treatments can be difficult to measure using standard imaging techniques, as changes in tumor size may not accurately reflect response. Liquid biopsies, on the other hand, offer the potential to measure ctDNA as an indicator of immunotherapy response, providing a new approach for monitoring treatment efficacy.
The clinical trial, known as BR.36, enrolled 50 patients with advanced or metastatic non-small cell lung cancer. These patients underwent liquid biopsies at various timepoints during treatment, using next-generation sequencing technology to analyze ctDNA. The results showed that ctDNA responses were detected early, within an average of eight weeks after treatment initiation. A ctDNA response, meaning no detectable ctDNA in the blood, corresponded to tumor shrinkage as observed through imaging. However, there were cases where ctDNA response was a more accurate predictor of survival, particularly for patients whose disease remained stable according to imaging.
Patients who had a ctDNA response had a longer progression-free survival and overall survival compared to those who did not. The difference in progression-free survival was 2.6 months versus 5.03 months, indicating the potential clinical benefit of ctDNA analysis in guiding treatment decisions.
The researchers hypothesized that liquid biopsies could provide rapid and accurate predictions of treatment outcomes. The results of the first stage of the BR.36 trial supported this hypothesis, leading to the initiation of the second stage. In this phase of the trial, patients’ treatment plans were tailored based on their ctDNA responses after two cycles of pembrolizumab, an immunotherapy drug. Patients with a high risk of disease progression were randomized to receive intensified treatment with pembrolizumab and chemotherapy or to continue with pembrolizumab alone.
The Cancer Research Institute, which invested in the second stage of the trial, anticipates that if the primary endpoint is met, the ctDNA detection assay used in the BR.36 study could gain approval. This may lead to liquid biopsies becoming the standard method for assessing the response to cancer immunotherapies in patients with non-small cell lung cancer.
The potential clinical benefit of ctDNA monitoring is promising, providing valuable information for treatment recommendations and potentially improving patient outcomes. A larger trial is planned to further validate the findings of the BR.36 study and to evaluate the utility of ctDNA monitoring in a broader patient population.
The results of this study highlight the potential of liquid biopsies in guiding treatment decisions and monitoring the response to immunotherapies. Further research and clinical trials are needed to fully establish the role of liquid biopsies in precision medicine and personalized cancer treatment.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
