Liquid biopsy cuts time to treatment by 37% for those with suspected advanced lung cancer
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Key takeaways:
- Those who received ctDNA testing before tissue diagnosis had median time to treatment of 39 days vs. 62 days for a reference cohort.
- The impact on clinically meaningful outcomes has yet to be determined.
Circulating tumor DNA genotyping before tissue diagnosis of suspected advanced non-small cell lung cancer resulted in significantly shorter median time to treatment compared with standard tissue testing, study results showed.
Time from sample collection to genotyping occurred more than three times faster with plasma circulating tumor DNA (ctDNA) testing compared with sequencing of tissue samples, according to data published in JAMA Network Open.
Background
Treatment of NSCLC requires knowledge of how to leverage actionable genomic alterations as part of the overall strategy, according to Miguel García-Pardo, MD, and colleagues in the division of medical oncology and hematology at Princess Margaret Cancer Centre in Toronto.
Delays in genotyping results — along with often incomplete results — are major barriers to personalizing cancer treatment, they wrote.
“Plasma ctDNA testing has shown clinical utility as a complementary tool in NSCLC molecular diagnosis, especially when tissue or time for molecular profiling is limited,” García-Pardo and colleagues added. “Although considered a valid tool for genotyping, the optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear.”
Methodology
Investigators designed ACCELERATE — a nonrandomized single-group study conducted at Princess Margaret Cancer Centre between July 1, 2021, and Nov. 30, 2022 — to evaluate the impact of ctDNA genotyping before a tissue diagnosis of suspected NSCLC on time to treatment.
The trial included 150 patients (median age, 68 years; range, 33-91; 53% men) referred for tissue confirmation of a lung cancer diagnosis after radiographic evidence of advanced disease.
Study participants underwent plasma ctDNA testing using a next-generation sequencing assay prior to standard-of-care confirmation with next-generation sequencing of a subsequent tissue biopsy.
Investigators compared results from the ACCELERATE cohort with a reference group of consecutive patients from Princess Margaret Cancer Centre who underwent next-generation genotyping after tissue diagnosis of NSCLC between 2018 and 2019.
Time from referral to treatment served as the study’s primary endpoint. Secondary endpoints included frequency of actionable targets identified using plasma ctDNA, time to sample collection, and turnaround time of plasma vs. tumor tissue profiling for patients with advanced nonsquamous NSCLC.
Key findings
Ninety patients (60%) had a confirmed diagnosis of advanced nonsquamous NSCLC.
Patients enrolled in the ACCELERATE cohort had significantly shorter median time to treatment compared with the reference cohort (39 days vs. 62 days; P < .001).
Investigators reported median turnaround time from sample collection to genotyping of 7 days (interquartile range, 6-9) for next-generation sequencing of plasma compared with 23 days (interquartile range, 18-28) for next-generation sequencing of tissue samples (P < .001).
Among 90 patients with a confirmed diagnosis of advanced nonsquamous NSCLC, 21 (23%) began targeted therapy before receiving results from next-generation sequencing of their tissue sample, and 11 (12%) harbored actionable alterations identifiable only through plasma ctDNA testing, according to the researchers.
Clinical implications
Results of the ACCELERATE trial suggest an association between use of liquid biopsy before tissue diagnosis of lung cancer and shortened time to treatment, according to García-Pardo and colleagues.
Additionally, plasma testing detected a higher rate of actionable genetic alterations compared with a cohort of patients who did not undergo a preconfirmatory liquid biopsy.
“Complementing standard tissue testing with plasma testing before diagnosis could increase access to precision medicine and may improve patient outcomes,” they wrote. “Although we believe this is a promising strategy to improve the diagnostic journey and treatment decision-making for patients with advanced NSCLC, the effect of this approach on clinically meaningful outcomes, such as quality of life, survival, and cost-effectiveness, still needs to be demonstrated.”
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