Dr Forde on ctDNA and MRD Testing in NSCLC

“There are patients who appear to be negative for ctDNA, but they’re still having a relapse of cancer. I’m not sure that [ctDNA] can be used in the adjuvant setting at the moment based on the current technology.”

Patrick Forde, MBBCh, PhD, the Patrick Prendergast Professor of Clinical Immuno-Oncology at the Trinity St James’s Cancer Institute, Trinity College Dublin, a consultant medical oncologist at St James’s Hospital in Dublin, and a professor at Johns Hopkins University, discussed where circulating tumor DNA (ctDNA) testing stands as a tool for guiding perioperative therapy in non–small cell lung cancer (NSCLC), and previewed ongoing perioperative trials at the 44th Annual PER® Chemotherapy Foundation Symposium.

Liquid biopsy technology continues to improve, but ctDNA testing is not yet ready for routine perioperative use, Forde said. Retrospective analyses of several phase 3 trials have examined ctDNA during neoadjuvant treatment as a predictor of long-term outcomes and suggest some prognostic value, he explained. Patients who clear ctDNA early during neoadjuvant therapy are likely to fare better than those who do not, according to Forde.

However, the technology may not be sensitive enough after surgery, Forde noted. In patients who received neoadjuvant chemoimmunotherapy followed by resection, the ctDNA detection rate in the adjuvant setting is only about 10% to 15%, even though a larger share of patients will relapse, he said. As a result, some ctDNA-negative patients still experience recurrence.

Forde said a range of phase 2 and 3 perioperative trials are ongoing, though results are likely some time away. Notable efforts include intensification strategies with personalized mRNA vaccines, he noted. KRAS G12C inhibitors, which have shown encouraging activity in advanced disease, are also moving into the perioperative setting, Forde said. In these studies, patients without a pathologic complete response after neoadjuvant chemoimmunotherapy and surgery are randomly assigned to a KRAS G12C inhibitor or continued immunotherapy, he noted. It will be a few years before final data are available, Forde concluded.