Measuring cancer DNA in the blood may give clinicians a better idea of which patients with lung cancer need their immunotherapy treatment altered.
A blood test may be helpful in determining which patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy treatment may benefit from additional drugs, according to findings from the phase 2 BR.36 trial published in the journal Nature Medicine.
The blood test is called a liquid biopsy and can detect the DNA of dying cancer cells — known as circulating tumor DNA or ctDNA — within the bloodstream. According to thee study findings, ctDNA analyses may be able to determine if a patient is experiencing an early response to immunotherapy and/or if they need more medications.
“There is an unmet clinical need to implement real-time, minimally invasive molecular analyses to understand patients’ responses to cancer treatments and guide clinical decision-making,” says lead study author Dr. Valsamo “Elsa” Anagnostou, director of the thoracic oncology biorepository at Johns Hopkins, leader of Precision Oncology Analytics, co-leader of the Johns Hopkins Molecular Tumor Board and co-director of the Lung Cancer Precision Medicine Center of Excellence, said in a press release.
The BR.36 trial included 50 patients with advanced or metastatic NSCLC, the majority of which (92%) had no prior anti-cancer treatments. Participants received the immunotherapy drug, Keytruda (pembrolizumab) via infusion every three weeks and then every six weeks for 24 months or until they experienced unacceptable side effects or until imaging tests revealed that they had disease progression.
Findings showed that by testing ctDNA through a process called next-generation sequencing, clinicians were able to detect if patients’ disease was responding to immunotherapy treatment within an average of eight weeks from starting the therapy.
“ctDNA response is particularly informative to understand the complexity of stable disease on imaging, which represents a sizable fraction of patients in whom imaging fails to timely and accurately detect the magnitude of therapeutic response,” Anagnostou said.
Of note, patients who had a ctDNA response, meaning that ctDNA was not detected in the blood samples, tended to have longer progression-free survival (time from treatment until death or disease worsening) than those who did not have a ctDNA response, with averages at 2.6 months and 5.03 months, respectively. Additionally, the researchers found that those with a ctDNA response tended to have longer overall survival (time from treatment until death of any cause) as well, with an average overall survival not yet being met at the time of the study analysis.
“Our study demonstrates that ctDNA response correlated with tumor size seen on imaging, which is the gold standard for monitoring response to cancer treatments and seemed to be better correlated with survival. This suggests ctDNA could be used as a strategy to identify patients at high risk of disease progression who could benefit from a switch in their therapeutic regimen.”
After the first phase of the BR.36 trial, researchers started a second phase of the trial, which will look at the potential benefit of personalizing treatments for patients who have undergone two cycles of Keytruda based on their ctDNA responses. The researchers hope to use ctDNA responses to identify which patients were at high risk of disease progression. These patients will then randomly be assigned to receive continued Keytruda treatment or an intensification of the immunotherapy agent plus chemotherapy.
“ctDNA has the potential to improve our ability to advise patients on the best treatment options for them. It may be better than traditional imaging in determining changes to treatments or providing assurance that patients should continue their current treatment. Our initial study indicates promising results, and we will move forward with a larger trial to clearly show whether ctDNA monitoring provides useful information based on treatment recommendations,” Dr. Janet Dancey director of the Canadian Cancer Trials Group, said in the press release.
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