Thoracic Consolidation Radiotherapy for ES-SCLC Treated With Chemo-immunotherapy

Small Cell Lung Cancer Extensive Stage Clinical Trial

Official title: A Phase I Dose Escalation Study of Thoracic Consolidation Radiotherapy for Extensive-stage Small Cell Lung Cancer Patients Treated With Chemo-immunotherapy

Status Recruiting

Clinical Trial Summary

This study intends to recruit ES-SCLC patients with response to standard first-line chemo-immunotherapy to assess the safety of receiving different doses of consolidative thoracic radiotherapy.

Clinical Trial Description

Approximately two-thirds of Small-cell lung cancer (SCLC) patients are in the extensive stage (Extensive-Stage SCLC, ES-SCLC) at the time of diagnosis, and the 5-year survival rate of these patients is less than 5%. Before the immunotherapy era, the standard first-line treatment for ES-SCLC had been platinum-based chemotherapy regimens combined with etoposide.

Since treatment failure patterns revealed high probability of residual thoracic disease and high risk of progression of thoracic lesions after ES-SCLC chemotherapy, previous studies suggest that thoracic consolidation radiotherapy in ES-SCLC patients who are sensitive to first-line chemotherapy can reduce the risk of thoracic recurrence and improve overall survival time. Slotman et al. further conducted a phase III randomized controlled clinical study to explore the application of thoracic consolidation radiotherapy in ES-SCLC (CREST study). The CREST study results showed that in ES-SCLC patients who responded to chemotherapy and had residual thoracic lesions, thoracic residual lesion radiotherapy (30 Gy/1 0Fx) combined with prophylactic brain radiotherapy could reduce the risk of thoracic recurrence by 50% and increase the 2-year survival rate from 3% to 13%.

With the advent of the era of immunotherapy, the IMpower133 trial showed that the combination of atezolizumab and chemotherapy prolonged the median overall survival time of ES-SCLC patients compared with the chemotherapy alone group. In the CASPIAN study, the combination of dulvumab and chemotherapy also resulted in a survival benefit. The ASTRUM-005 study using PD-1 monoclonal antibody Serplulimab in combination with chemotherapy also achieved prolonged overall survival.

Although the overall median survival of ES-SCLC is prolonged after immunotherapy in combination with chemotherapy, patients who truly achieve long-term survival are still limited, with a 3-year OS rate of about 15% - 20%. Accordingly, it is necessary to explore effective methods to combine radiotherapy and maximize the benefit population of immunotherapy in ES-SCLC.

Failure pattern analysis revealed that, consistent with the era of non-immunotherapy, the main progression phenotype in patients receiving first-line chemotherapy + immunotherapy remained thoracic progression, suggesting that sequential thoracic consolidation radiotherapy is still likely to achieve clinical benefit in ES-SCLC patients receiving chemo-immunotherapy.

Immunotherapy combined with concurrent chemoradiotherapy has shown good safety and survival benefit in limited-stage SCLC. In non-small cell lung cancer (NSCLC), the safety of sequential immunotherapy after thoracic chemoradiotherapy has also been verified. However, there is a lack of prospective studies to investigate the safety of sequential thoracic consolidation radiotherapy after first-line immunochemotherapy in ES-SCLC patients.

At present, the widely used ES-SCLC thoracic consolidation radiotherapy regimen is based on the 30 Gy/1 0Fx dose fractionation of CREST study. At the same time, it has been shown that increasing the dose of single radiotherapy within a certain range helps to increase the production of immunogenic death by tumor cells, that is, more tumor-specific antigens that can be recognized by the immune system are produced during the induction of tumor cell death. Therefore, this study intends to perform a dose escalation study based on 30 Gy/10Fx dose fractionation and assess the safety of this treatment mode. ;

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer Extensive Stage
• Small Cell Lung Carcinoma

• NCT number: NCT06187740
• Study type: Interventional
• Source: Fudan University
• Contact: Xiao Chu
• Phone: 15821383376
• Email: chuxiao@sibs.ac.cn
• Status: Recruiting
• Phase: Phase 1
• Start date: December 1, 2023
• Completion date: December 31, 2025