536P - Safety and efficacy of silibinin in patients with brain metastases after stereotactic radiosurgery (SRS): The SUSTAIN trial

Background

Brain metastases (BMs) account for more than one-half of all intracranial tumors. In recent years, stereotactic radiosurgery (SRS) has become the mainstay of BMs treatment, providing high rates of local tumor control. Nevertheless, SRS alone is associated with a 30-50% risk of distant brain failure (DBF), consequently requiring careful follow-up and possible rescue treatments. Silibinin or silybin, a natural polyphenolic flavonoid, has shown promising antitumor activity, leading to improvement of BMs in patients with progressive non-small cell lung cancer. Therefore, our exploratory study aims to evaluate whether the use of a silibinin-based nutraceutical (SILLBRAIN, HEALTH4U S.r.l.) can significantly reduce DBF rate at 6 months in patients with first-diagnosed BMs treated with SRS with or without surgery.

Methods

SUSTAIN is an interventional, prospective, single-arm, phase II study. A total of 80 patients treated in our institution are planned to be enrolled. Patients receive 2 capsules of SILLBRAIN per day for the first month after SRS and 1 capsule per day thereafter. Primary endpoints are 6-month distant brain failure (DBF) rate and safety.

Results

Thirty patients have been enrolled at the time of the primary analysis. NSCLC and breast cancer were the prevalent histologies. Overall, the number of treated lesions was 73, with a median of 1 lesion (range 1-9). All patients underwent SRS, with a median prescription dose and a median prescription isodose line of 24 Gy and 80%, respectively. After a 14-month enrollment period, with a median follow-up of 9 months, 6 patients reported DBF according to RANO-BM criteria, with a 6-month DBF rate of 20%. Only 1 treated lesion met the criteria for progression, accounting for a 6-month local control (LC) rate of 98%. Six patients died, with a 6-month OS rate of 80%. Two patients discontinued SILLBRAIN assumption due to G1 nausea. No other adverse events were reported.

Conclusions

At about half of our enrollment target, the results show a favorable trend towards 6-month DBF rate reduction. Toxicity proved manageable, consistent with the literature and limited to gastrointestinal effects. A larger sample and longer follow-up are needed to confirm our hypothesis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.