Circulating Tumor DNA Test Identifies Complete Immunotherapy Responders

However, clinicians remain uncertain about how long therapy should continue, as imaging cannot confirm molecular clearance. New real-world data suggest that circulating tumor DNA monitoring may help identify complete molecular responders during first-line immunotherapy.

Natera’s Signatera test was evaluated in a real-world analysis presented at the Society for Immunotherapy of Cancer Annual Meeting, held November 4–8 in Phoenix, Arizona. The analysis included 424 patients receiving first-line immunotherapy for stage IV melanoma, renal cell carcinoma, microsatellite instability-high colorectal cancer, or non-small cell lung cancer. Complete molecular responders were defined as patients who achieved two consecutive negative Signatera results.

Signatera was used to assess molecular response by measuring circulating tumor DNA clearance during treatment. Complete molecular responders had a 36-month overall survival rate of 93.2%, compared with 77.9% among all other patients, corresponding to a hazard ratio of 0.24 and a P value of 0.0003. Across individual tumor types, 36-month overall survival among complete molecular responders ranged from 83.1% in non-small cell lung cancer to 100% in microsatellite instability-high colorectal cancer.

The analysis also compared complete molecular responders who continued immunotherapy with those who discontinued treatment early. Overall survival was 93.5% among patients who remained on treatment and 89.4% among those who stopped early, with no significant difference in survival between the groups. Natera stated that its tests are supported by more than 400 peer-reviewed publications and that its laboratories operate with ISO 13485 certification, College of American Pathologists accreditation, and CLIA certification.

“For patients with metastatic cancer who achieve a durable response, deciding how long to continue immunotherapy is one of the most difficult clinical decisions,” said Meghan J. Mooradian, MD, Cutaneous Medical Oncology, Mass General Brigham Cancer Institute, and lead author of the study. “Because imaging alone may not fully capture whether disease has been completely cleared, our findings support further investigation of molecular response as a biomarker to help personalize treatment duration and identify patients who may discontinue therapy early.”

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