Friends’ recent circulating tumor DNA (ctDNA) study examined 8 clinical trials including 940 patients with advanced non-small cell lung cancer (aNSCLC) treated with tyrosine kinase inhibitors (TKI) to assess whether changes in ctDNA levels could serve as an early indicator of overall survival (OS) and progression-free survival (PFS). The study investigated the association between ctDNA clearance (i.e., transitioning from detected ctDNA at baseline, prior to treatment, to non-detected on treatment) and improved long-term clinical outcomes such as OS and PFS, with the goal to evaluate whether ctDNA can serve as an early endpoint in future oncology drug development. The study also assessed how early RECIST measurements, commonly used in clinical trials to determine tumor response as an early indicator of long-term clinical outcomes, taken within 10 weeks of treatment initiation correlated with changes in ctDNA.
The study found that patients with ctDNA clearance within the first 10 weeks of treatment had better OS and PFS outcomes than patients who had persistent detection. Additionally, changes in ctDNA can offer predictive insights for patients with Stable Disease (SD) and Partial Response (PR) as determined by early RECIST measurements. These early RECIST measurements can be ambiguous due to limitations of radiological imaging, as images may not clearly indicate whether a tumor is shrinking enough to suggest treatment efficacy or if it is merely stable and not responding.
Why This Research Matters
ctDNA holds promise as an efficient, non-invasive biomarker for monitoring the efficacy of cancer treatments in oncology clinical trials. By generating data that characterizes the relationship between change in ctDNA levels and clinical outcomes, this research, along with the body of growing literature on the subject, supports future use of ctDNA assessments as an early endpoint in clinical trials. Early endpoints are important for predicting clinical benefit in support of Accelerated Approval, which ensures beneficial drugs get to patients faster. Ultimately, this work builds on the growing body of evidence to facilitate timely access to innovative treatments for patients with cancer by using ctDNA, ultimately addressing patient unmet medical needs.
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