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Across a wide spectrum of cancers, advanced testing methods are making headway in measuring circulating tumor DNA (ctDNA) and other biomarkers to assess molecular treatment responses in patients, laying the path for more effective and targeted therapies.
The arena of kidney cancer has seen such progress. At the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, researchers unveiled the first-ever molecular test that predicts immunotherapy treatment response for this disease.
Known by its trade name CLEARScore, the test derives from the expression of eight genes in clear cell renal cell cancer tumors, classifying kidney cancer by molecular type. Using it to investigate anti-programmed death ligand 1 (PD-L1) checkpoint inhibitors and immune cell markers in 36 kidney cancer patients, researchers found that for a subset of patients, the eight-gene score correlated with immune cell infiltration and clinical response.
“Immunotherapy is a major breakthrough in our battle against kidney cancer. It is, however, expensive and may have side effects. Having a test that can distinguish whether a kidney cancer patient will or will not benefit from anti-PD-L1 immunotherapy would be of high clinical value,” said study designer and lead author Ravindran Kanesvaran, MD, senior consultant with the National Cancer Centre Singapore’s Department of Medical Oncology, in a statement.
Other recent studies have looked at quantifying PD-L1 protein levels in tumors to personalize cancer treatments. In one clinical trial, which enrolled 475 patients with PD-L1-positive advanced solid tumors, researchers found that PD-L1 expression either alone or in combination with two other biomarkers, T-cell-inflamed gene-expression profiling and tumor mutational burden, could help identify patients most likely to respond to anti-PD-1 therapies across 20 cancer tumor types. Another study in The Journal of Molecular Diagnostics used a minimally invasive bronchoscopy technique to analyze small, unfixed tissue specimens and identify non-small-cell lung cancer (NSCLC) in patients. Isolating RNA and DNA from the samples, researchers used an assay to diagnose tumor malignancy and PD-L1 status just hours after collecting the specimens.
Quantifying PD-L1 transcript levels can help determine the therapy path of NSCLC patients. For example, those with lower PD-L1 expression levels are more likely to benefit from chemotherapy combined with anti-PD-1 antibody pembrolizumab. “The emergence of lung cancer screening trials will result in greater demand to define the molecular nature of suspect lung nodules. This test has the potential to save considerable time and money in identifying patients who are most likely to benefit from checkpoint inhibitors such as pembrolizumab,” said Steven Bozinovski, PhD, of the School of Health and Biomedical Sciences at RMIT University in Bundoora, Victoria, Australia, in a statement.
Blood-based liquid biopsy has also proved its worth in tracking treatment responses in lung cancer patients. One study used this method to identify ctDNA and track tumor burden in 28 NSCLC patients treated with osimertinib, mavelertinib, afatinib, or erlotinib. Liquid biopsy detected patient response to treatment about a month earlier and with more accuracy than computerized tomography imaging. Sixteen patients who had responded to treatment had almost no ctDNA in their blood. Conversely, researchers found few changes to ctDNA levels in eight patients who hadn’t responded to therapy. These individuals also had much shorter progression-free survival rates.
In a separate study of 38 patients with NSCLC, researchers measured ctDNA and immune blood cell changes to determine tumor responses to anti-PD-1 therapy, achieving results more than 2 months earlier than seen with conventional imaging. Overall, they were better able to predict survival by tracking molecular response. Similar to Bozinovski’s study, survival rates were higher in molecular responders.
“Early detection of disease progression on immunotherapy opens a window of opportunity in which changes in liquid biopsies may allow patients with resistance to be rapidly identified and redirected to receive alternative therapies,” said Valsamo Anagnostou, MD, PhD, assistant professor of oncology at the Johns Hopkins University School of Medicine in Baltimore, in a statement.