Measuring circulating tumor (ct) DNA after induction chemotherapy could identify the best candidates for consolidation immunotherapy among patients with limited-stage small cell lung cancer (SCLC), according to research presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.
“This is the first study to show that early ctDNA detection after induction chemotherapy can help identify patients who are more likely to benefit from consolidation immunotherapy,” said Nan Bi, MD, from the Chinese Academy of Medical Sciences. “It’s a step toward precision immunotherapy in limited-stage SCLC.”
Bi and team analyzed 490 serial plasma ctDNA samples from 144 patients (77% men) with limited-stage SCLC. Of these, 100 received two cycles of induction chemotherapy followed by concurrent chemoradiotherapy, and 44 were given chemoradiotherapy plus consolidation immunochemotherapy with serplulimab.
The researchers found that, overall, ctDNA dynamics predict disease progression or death. Indeed, patients with positive ctDNA after induction chemotherapy but before radiotherapy (t1) had a significant 2.46-fold higher risk for disease progression or death than those with negative ctDNA.
Specifically, median progression-free survival (PFS) was 11.4 months in the patients with positive ctDNA compared with 49.4 months among those with negative ctDNA at t1.
Similar results were observed for ctDNA levels measured post radiotherapy (t2), with the risk for disease progression or death 2.20-fold higher in people with positive versus negative ctDNA and median PFS at 12.4 and 42.2 months, respectively.
When the researchers separated the patients by the type of treatment given, they found that ctDNA status at t1 could identify patients likely to benefit from consolidation immunotherapy.
Bi reported that individuals with positive ctDNA at t1 who received consolidation immunotherapy had a significant 71% lower risk for disease progression or death than those who only received chemoradiotherapy, with median PFS not reached in the former group and 11.4 months in the latter.
For overall survival (OS), the risk for death was a significant 95% lower among ctDNA-positive patients at t1 who did versus did not receive consolidation immunotherapy, with median OS not reached and 28.1 months, respectively.
By contrast, there was no significant difference in PFS or OS between the patients who did and did not receive consolidation immunotherapy and had negative ctDNA at t1, suggesting that ctDNA-negative patients derived no significant benefit from consolidation immunotherapy.
Bi then showed that combining ctDNA status with radiologic tumor response further refines prognosis.
“Most importantly, we developed a three-level prognostic stratification strategy by integrating early ctDNA status and radiological tumor shrinkage to distinguish patients who benefit from the addition of consolidation immunotherapy,” she remarked.
Patients with the highest risk, that is, those with positive ctDNA and tumor shrinkage of less than 60% after two cycles of induction chemotherapy, had a significant 71% lower risk for disease progression or death and a significant 92% lower risk for death when they received consolidation immunotherapy.
Conversely, patients with low risk (ctDNA-negative, ≥60% tumor shrinkage) or medium risk (ctDNA-negative, <60% tumor shrinkage or ctDNA-positive, ≥60% tumor shrinkage) derived no significant PFS or OS benefit from consolidation immunotherapy.
Bi said that the findings “offer a compelling rationale for integrating ctDNA-based stratification in future LS-SCLC trials and may help guide real-time decisions on the use of consolidation immunotherapies.”
She added that a large-scale independent prognostic study to find the value of the ctDNA monitoring is now warranted in these patients, but cautioned that the current costs of ctDNA testing may limit widespread adoption.