Loading ...

Circulating tumor DNA (ctDNA) may help personalize the use of consolidation immunotherapy in patients with limited-stage small cell lung cancer (LS-SCLC), according to a study from China. 

Researchers found that among patients with LS-SCLC treated with chemoradiotherapy, those who were ctDNA-positive after induction chemotherapy had significantly better survival outcomes if they also underwent consolidation immunotherapy. In contrast, patients who were ctDNA-negative after chemotherapy derived no added benefit from immunotherapy. 

The study, led by Nan Bi, MD, PhD, from the National Cancer Center of China and the Chinese Academy of Medical Sciences, Beijing, was featured at a press briefing at the World Conference on Lung Cancer 2025.

Based on the findings, ctDNA monitoring “represents a potentially meaningful clinical advance in the field,” said briefing moderator Brendon Stiles, MD, professor and chief of thoracic surgery and surgical oncology at Montefiore Einstein, Bronx, New York. 

Concurrent chemoradiotherapy plus consolidation immunotherapy is now considered standard of care for LS-SCLC following results of the phase 3 ADRIATIC trial.

However, Bi said, biomarkers that can help predict patients’ response to immunotherapy and potentially guide treatment decisions have been lacking

To investigate a possible role for ctDNA, Bi’s team analyzed data on 144 patients with LS-SCLC: 100 treated with chemoradiotherapy alone and 44 treated with chemoradiotherapy plus consolidation immune checkpoint inhibitor therapy (serplulimab) as part of two clinical trials. Overall, 77% of the cohort was male, 66% were current/former smokers, and 90% had stage III disease at diagnosis. 

Patients’ ctDNA samples were collected at baseline; after induction chemotherapy but before radiotherapy; after radiotherapy; and during immunotherapy surveillance at 3 months, 6 months, and 1 year. 

In the overall cohort, the study found patients who still had detectable ctDNA after induction chemotherapy had a worse outlook, with a median progression-free survival (PFS) of 11.4 months vs 49.4 months among patients who were ctDNA-negative (hazard ratio [HR], 2.46; P < .001).

Moreover, that early ctDNA status identified patients who did or did not benefit from consolidation immunotherapy. Among patients who were ctDNA-positive after induction chemotherapy, immunotherapy significantly improved both PFS (HR, 0.29; P = .013) and overall survival (OS) (HR, 0.05; P < .001). In contrast, patients who were ctDNA-negative post-induction showed no additional benefit from immunotherapy in terms of PFS (HR, 1.30; P = .428) or OS (HR, 1.14; P = .776). 

The researchers also found that combining ctDNA status with radiologic tumor response helped to further refine prognosis, with three risk categories emerging (low, mid, and high). Patients in the low-risk group were ctDNA-negative and had at least 60% tumor shrinkage; their prognosis was excellent, Bi said, and immunotherapy brought little additional benefit.

High-risk patients were ctDNA-positive with less than 60% tumor shrinkage, and they experienced significant survival improvements with consolidation immunotherapy (PFS: HR, 0.24; OS: HR, 0.06).

The picture was less clear, however, for patients in the mid-risk group. Their prognosis was better than that of high-risk patients, and the additional benefit of immunotherapy was uncertain, Bi reported. “This group requires further exploration,” she told conference attendees.

According to Bi, the findings strongly support integrating ctDNA-based stratification into future clinical trials of patients with SCLC; but the approach is not yet ready for adoption in the clinic.

“For now, we don’t have high-grade evidence for clinical use of ctDNA monitoring in clinical practice and more research is needed,” she said. “I think in the future, after evidence from a prospective study, we can use this to guide our consolidation therapy.” 

The study had commercial funding. A co-author was with Nanjing Geneseeq Technology Inc.