BioPharma, Diagnostics

Another study shows liquid biopsy can detect cancer immunotherapy biomarker

The study, by Personal Genome Diagnostics and academic researchers, was able to predict responses to checkpoint inhibitor therapy in patients with MSI-H and high tumor mutational burden.

A new study indicates that liquid biopsy may provide a way to predict responses to the first drug to win a so-called tissue-agnostic cancer approval from the Food and Drug Administration.

Researchers from Baltimore-based liquid biopsy maker Personal Genome Diagnostics, Johns Hopkins University, New York’s Memorial Sloan Kettering Cancer Center and other institutions found that PGDx’s product was able to detect microsatellite instability, or MSI, in circulating tumor DNA and also to estimate the likelihood of an immediate and durable response to treatment with an immune checkpoint inhibitor. Merck & Co.’s PD-1 inhibitor Keytruda (pembrolizumab) received approval from the FDA for any solid tumor with high expression of MSI or mismatch repair deficiency, also known as MSI-H/dMMR, in 2017.

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A Deep-dive Into Specialty Pharma

A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.

“Microsatellite instability and high tumor mutation burden are promising pan-tumor biomarkers that are used to identify patients who may be candidates for treatment with immune checkpoint blockade,” PGDx vice president for translational medicine John Simmons said in a statement. “Obtaining samples via tumor biopsy can be challenging in people with advanced cancer, so this liquid biopsy test is a tool that can help doctors select the best therapy for their patients.”

The researchers obtained cell-free DNA samples from a combination of healthy donors and patients with metastatic cancer, showing a specificity greater than 99 percent, in 163 samples, according to an abstract of the study, published in Clinical Cancer Research. They found that sensitivity to MSI and high tumor mutation burden were respectively 78 percent and 67 percent. For patients who received a PD-1 inhibitor, the researchers demonstrated that MSI and high TMB in plasma prior to treatment predicted progression-free survival.

A study published last month in the same journal also showed that Guardant Health’s Guardant360 assay was able to detect MSI-H/dMMR at a rate comparable to that of standard tissue testing. That study was based on 1,145 cfDNA samples for which tissue MSI status based on tissue testing was available, with an overall accuracy of 98.4 percent and positive predictive value of 95 percent.

The challenge with liquid biopsy in general is to ensure that it does not produce too many false positive results, such that tissue biopsy would remain necessary to confirm them, experts have said. At the American Society of Clinical Oncology’s annual conference in June, an expert noted that even a 1 percent false-positive rate would be cause for concern, as it would make it difficult for liquid biopsy to replace tissue biopsy if patients inevitably had to undergo both tests for confirmation.

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