Radiotherapy Plus Chemoimmunotherapy Improves Frontline ES-SCLC Prognosis

Combinations of anti-angiogenic therapy with chemoimmunotherapy may feasibly be shifted forward in real-world extensive-stage small cell lung cancer care.

Adding radiotherapy to first-line chemoimmunotherapy at initial diagnosis can improve patient prognosis for those with extensive-stage small cell lung cancer (SCLC), according to findings from a real-world study shared at the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting.

In the poster, the presenting study author, Jun Wang, MD, PhD, of the Department of Radiation Oncology at the Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Radiation Oncology, in Shijiazhuang, China, and coauthors noted that the frontline standard for patients with ES-SCLC is chemotherapy combined with immunotherapy. However, the investigators shared that this analysis was necessary because although “immunotherapy combined with chemotherapy has led to significant improvement in overall survival [OS] for [extensive-stage] SCLC, the survival benefit remains limited, underscoring the urgent need to explore novel combination treatment strategies.”

With a median follow-up of 29.9 months, the median OS of the overall patient population was 16.6 months, with 1- and 2-year OS rates of 65.2% and 33.3%. Furthermore, univariate analysis showed that the presence of baseline liver metastasis and whether radiotherapy was combined were factors related to OS. Baseline liver metastasis was an independent risk factor for OS (HR, 1.841; P = .002).

A subgroup analysis of chemoimmunotherapy combined with radiotherapy did not show a significant difference in the median OS between the group combined with thoracic radiotherapy and the group without combination, with median OS values of 21.0 months vs 18.9 months, respectively (P = .257).

Those who received treatment combined with prophylactic cranial irradiation experienced an intracranial progression rate of 18.2% vs 51.3% among those who received therapy not combined with prophylactic cranial irradiation(P = .727). The median OS was 30.7 months vs 15.0 months, respectively (P = .033).

Chemoimmunotherapy combined with anti-angiogenic agents achieved a median OS of 19.8 months in the first- and second-line of treatment compared with 18.9 months in the third-line of treatment (P = .046).

“In patients with extensive-stage [SCLC], the addition of radiotherapy to first-line [chemoimmunotherapy] treatment at initial diagnosis can improve patient prognosis. There is no significant trend of survival benefit with the combination of first-line chemoimmunotherapy and thoracic radiotherapy. However, the combination of first-line chemoimmunotherapy and prophylactic cranial irradiation can significantly reduce the rate of intracranial recurrence and significantly prolong OS,” Wang and coauthors wrote in the poster. “The OS of first/second-line anti-angiogenic treatment is better than that of third-line treatment, suggesting that the combination of anti-angiogenic treatment may be shifted forward in real-world practice.”

The analysis included a total of 163 patients with extensive-stage SCLC who received chemotherapy combined with immune checkpoint inhibitors as first-line therapy from September 2019 to June 2023 at the Fourth Hospital of Hebei Medical University. The collected data covered patient baseline characteristics, cycles of chemotherapy, metastatic organs and their numbers, categories of immune checkpoint inhibitors, and the combination treatment patterns of radiotherapy and anti-angiogenic drugs.

The primary aims of the trial were to evaluate the clinical efficacy and safety of adding radiotherapy or anti-angiogenic drugs to first-line chemoimmunotherapy in patients with newly diagnosed extensive-stage SCLC, to explore the value of multi-dimensional combined treatment, and to provide an evidence-based rationale for individualized treatment strategies.

Regarding safety, any-grade treatment-related adverse events (TRAEs) occurred in 93.3% of all patients, and grade 3 or 4 TRAEs occurred in 20.0% of patients. No treatment-related deaths were observed.

Reference

Li Q, Liu Q, Jun W, Wang J, Li B. Real-world study on the efficacy, safety, and prognostic analysis of chemotherapy combined with immunotherapy as first-line treatment for extensive-stage small cell lung cancer. Presented at the 2025 American Society of Radiation Oncology (ASTRO) Annual Meeting; September 27 – October 1, 2025; San Francisco, CA.