FDA Approves Y-90 Resin Microspheres for Unresectable HCC

US FDA

The FDA has approved SIR-Spheres Y-90 resin microspheres for the treatment of patients with unresectable hepatocellular carcinoma (HCC).1 It is indicated for patients with no macrovascular invasion, Child-Pugh A cirrhosis, well-compensated liver function, and good performance status.2

This regulatory decision was backed by data from the prospective, multicenter, open-label, single-arm DOORwaY90 study (NCT04736121), which investigated the first-line efficacy and safety of SIR-Spheres in patients with HCC.1,3 The trial enrolled 100 patients from 18 centers in the US and included 65 patients in the interim primary efficacy cohort.1

DOORwaY90 met its prespecified coprimary end points. The overall response rate (ORR) was 98.5% per independent central review, and all evaluable patients achieved a response, resulting in a local tumor control rate of 100%. Furthermore, the median duration of response (DOR) was longer than 300 days.

Moreover, SIR-Spheres had a favorable safety profile.

"This study moves the field of radioembolization forward with reproducible dosimetry outcomes and a strong safety profile linked to very positive clinical results," Armeen Mahvash, MD, an interventional radiologist in the Department of Interventional Radiology in the Division of Diagnostic Imaging at The University of Texas MD Anderson Cancer Center in Houston; as well as a co-principal investigator of the DOORwaY90 study, stated in the news release. "This will give multidisciplinary care teams the confidence to recommend SIR-Spheres for HCC treatment."

This approval expands the indication for SIR-Spheres, which was previously FDA approved for the treatment of patients with colorectal cancer (CRC) that has metastasized to the liver.

"The expanded indication makes SIR-Spheres the only Y-90 treatment approved in the US for both HCC and CRC," Matt Schmidt, chief executive officer of Sirtex Medical, the developer of SIR-Spheres, added in the news release. "This milestone reflects our ongoing commitment to delivering flexible, personalized therapies—with multiple dose options available daily—that empower physicians to treat patients when and where it works best."

Y-90 resin microspheres deliver a lethal dose of radiation to tumors but spare surrounding healthy tissue.4 DOORwaY90 enrolled patients at least 18 years of age with unresectable/unablatable HCC; Barcelona Clinic Liver Cancer stage A, B1, B2, or C disease; a maximal tumor diameter of 8 cm; a sum of maximal tumor diameters of 12 cm or less; and at least 1 tumor measuring at least 2 cm on the long axis per localized, modified RECIST criteria. Patients also needed to have a life expectancy of at least 6 months, a baseline Child-Pugh score of A5 or A6, and a baseline ECOG performance score of 0 or 1. Patients also needed to be treatment naive or have developed a new lesion following prior locoregional liver resection with negative pathological margins, no microvascular invasion, and no recurrence at resection margins for at least 6 months post-treatment and no new lesions within 6 months of liver resection; or following prior ablation of a single lesion measuring at least 3 cm with no recurrence of the treated lesion for at least 6 months post-treatment. For safety considerations, at least 33% of the patients' total liver volume (based on body surface area) needed to be disease free and not treated with Y-90.

The trial's coprimary end points were best ORR and DOR. Secondary end points included the incidence of grade 3 or higher toxicity, quality of life, and the incidence of liver resection and transplantation post-treatment.

Patients received biocompatible resin microspheres containing Y-90 as an injectable permanent implant preferentially placed into the distal microvascular supply of tumors.4 The spheres were between 20 microns and 60 microns in diameter.

References

1. Sirtex Medical’s SIR-Spheres Y-90 resin microspheres receive FDA approval for the treatment of unresectable hepatocellular carcinoma. News release. Sirtex Medical. July 7, 2025. Accessed July 7, 2025. https://www.sirtex.com/us/news/press-releases/news-item?id=11510
2. SIR-Spheres Y-90 resin microspheres. Prescribing information. July 7, 2025. Accessed July 7, 2025. https://www.sirtex.com/Media/55rprxv2/SSL-US-17%20SIR-Spheres%20US-IFU%20R4.pdf
3. Mahvash A, Chartier S, Turco M, et al. A prospective, multicenter, open-label, single-arm clinical trial design to evaluate the safety and efficacy of 90Y resin microspheres for the treatment of unresectable HCC: the DOORwaY90 (Duration Of Objective Response with arterial Ytrrium-90) study. BMC Gastroenterol. 2022;22(1):151. doi:10.1186/s12876-022-02204-1
4. Selective internal radiation therapy (SIRT) using SIR-Spheres Y-90 resin microspheres on DoR & ORR in unresectable hepatocellular carcinoma patients (DOORwaY90). ClinicalTrials.gov. Updated February 5, 2025. Accessed July 7, 2025. https://clinicaltrials.gov/study/NCT04736121