Circulating tumor DNA dynamics predict benefit from consolidation immunotherapy in locally advanced non-small-cell lung cancer

Circulating tumor DNA (ctDNA) molecular residual disease (MRD) following curative-intent treatment strongly predicts recurrence in multiple tumor types, but whether further treatment can improve outcomes in patients with MRD is unclear. We applied cancer personalized profiling by deep sequencing (CAPP-Seq) ctDNA analysis to 218 samples from 65 patients receiving chemoradiation therapy for locally advanced non-small-cell lung cancer, including 28 patients receiving consolidation immune checkpoint inhibition (ICI). Patients with undetectable ctDNA after chemoradiation therapy had excellent outcomes whether or not they received consolidation ICI. Among such patients, one died from consolidation ICI-related pneumonitis, highlighting the potential utility of only treating patients with MRD. In contrast, patients with MRD after chemoradiation therapy who received consolidation ICI had significantly better outcomes than patients who did not receive consolidation ICI. Furthermore, the ctDNA response pattern early during consolidation ICI identified patients responding to consolidation therapy. Our results suggest that consolidation ICI improves outcomes for non-small-cell lung cancer patients with MRD and that ctDNA analysis may facilitate personalization of consolidation therapy.