2189P - Combining SBRT with GM-CSF and Peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors

Background

After the failure of multi-line treatment, patients with stage Ⅳ thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis.

Methods

We conducted this open-label, single-arm, phase Ⅱ trial to evaluate SBRT plus GM-CSF and Peg-IFNα in previously treated patients with stage Ⅳ thymic tumors. A 21-day treatment cycle consisted of SBRT delivered to one metastatic lesion with 30 Gy in 5 fractions from day 1, synchronous subcutaneous injection of GM-CSF 125 μg/ m² once daily for 14 days, and subcutaneous injection of Peg-IFNα 90 μg on day 8. If the patient has more than two metastatic lesions, another treatment cycle was repeated. After the completion of 1 or 2 treatment cycles, Peg-IFNα therapy was maintained for at least half a year with a subcutaneous injection of 90 μg once a month. The two primary endpoints were the proportion of patients with abscopal effects and the objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), and therapeutic safety.

Results

A total of 20 patients from March 2021 to September 2022, were enrolled in this trial, with 1 (5.0%) type A thymoma, 2 (10.0%) type B1 thymoma, 2 (10.0%) type B2 thymoma, 1 (5.0%) type B3 thymoma, 12 (60.0%) thymic squamous cell carcinoma and 2 (10.0%) thymic neuroendocrine tumor. At a median follow-up of 18.6 months, 8 (40.0%) out of 20 patients had abscopal effects, and the ORR was 45.0%.The median OS had not been attained yet. The median PFS was 9.0 months. We observed that patients with abscopal effects tended to have longer OS and PFS than those without abscopal effects. 3 patients (15.0%) experienced Grade 3 treatment-related adverse events (CTCAE version 5.0), among which cardiac insufficiency compelled 1 patient to drop out of treatment.

Conclusions

Combining SBRT with GM-CSF and Peg-IFNα was well tolerated with acceptable toxicity and may represent a promising salvage therapy for previously treated patients with stage Ⅳ thymic tumors. The occurrence of abscopal effects is likely to improve patient outcomes.

Clinical trial identification

NCT04517539.

Editorial acknowledgement

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

Clinical Research Plan of SHDC (No. SHDC2020CR3025B).

Disclosure

All authors have declared no conflicts of interest.