FDA Approves SIR-Spheres Y-90 for First-Line Use in Unresectable HCC

• The FDA has granted approval to SIR-Spheres Y-90 resin microspheres in unresectable hepatocellular carcinoma (HCC).
• Findings from the DOORwaY90 study (NCT04736121) support this approval.
• SIR-Spheres was previously approved by the FDA for the treatment of patients with colorectal cancer (CRC) that has metastasized to the liver.

The FDA has expanded the indication for SIR-Spheres Y-90 resin microspheres to include the first-line treatment of patients with unresectable HCC.¹

The approval is based on findings from the DOORwaY90 study, a prospective, multicenter, single-arm trial that evaluated the efficacy and safety of SIR-Spheres in 100 patients with unresectable HCC. Among the 65 patients in the primary efficacy cohort, the overall response rate (ORR) was 98.5% per independent central review, local tumor control was achieved in 100% of evaluable patients, and the median duration of response exceeded 300 days.²

The study also showed a favorable safety profile, making it a compelling first-line option, especially in patients who require localized treatment with minimal systemic toxicity.

"This study moves the field of radioembolization forward with reproducible dosimetry outcomes and a strong safety profile linked to very positive clinical results," said 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, in a press release.¹ "This will give multidisciplinary care teams the confidence to recommend SIR-Spheres for HCC treatment."

SIR-Spheres deliver targeted internal radiation directly to liver tumors while sparing healthy surrounding tissue. SIR-Spheres are administered via hepatic artery injection and consist of biocompatible resin microspheres containing Yttrium-90. The microspheres are 20 to 60 microns in diameter and act as a permanent implant delivering high-dose, localized radiation.

This expanded approval adds to the existing indication for metastatic CRC with liver metastases, making SIR-Spheres the only FDA-approved Y-90 therapy in the US for both HCC and mCRC.

"The expanded indication makes SIR-Spheres the only Y-90 treatment approved in the US for both HCC and mCRC," Matt Schmidt, chief executive officer of Sirtex Medical, the developer of SIR-Spheres, added in the press 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."

About the DOORwaY90 Study

The DOORwaY90 enrolled patients aged 18 years and older with unresectable/unablatable HCC with Barcelona Clinic Liver Cancer stage A, B1, B2, or C disease, and a maximal tumor diameter of 8 cm, with total tumor burden ≤12 cm.³ Patients were required to have at least 1 tumor measuring at least 2 cm on the long axis per localized, modified RECIST criteria; a life expectancy of at least 6 months; an ECOG performance status of 0 or 1; and a baseline Child-Pugh score of A5 or A6. Patients enrolled also were required to be treatment naive or with controlled prior liver-directed therapy.

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

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://tinyurl.com/yc75an7s

2. 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-

3. 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