Personalized Dosimetry With Y-90 Glass Microspheres Shows Positive Activity in HCC

Personalized dosimetry with TheraSphere, the radioembolization therapy comprised of Yttrium-90 (Y-90)-containing glass microspheres, was well tolerated and showed promising overall survival (OS) data in patients with hepatocellular carcinoma (HCC), according to Etienne Garin, MD, PhD.

Data from an interim analysis of the PROACTIF French post-approval registry study demonstrated that patients with HCC (n = 670) who received Y-90 glass microspheres achieved a median OS of 20.8 months (95% CI, 18.3-23.3). Rates at 6-, 12-, 18-, and 24-months were 87.2% (95% CI, 84.2%-89.6%), 69.9% (95% CI, 65.8%-73.6%), 55.4% (95% CI, 50.8%-59.8%), and 44.7% (95% CI, 39.8%-49.5%), respectively. Additionally, 37 patients experienced serious adverse effects ([AEs] n = 42), 22 of which were device or procedure related. Treatment-emergent AEs (n = 60) occurred in 42 patients as well, 39 of which were device or procedure related.¹

“This is the only therapeutic approach with a treatment simulation allowing for good candidate selection and personalized treatment [with] dosimetry,” Garin, principal investigator of the study and a nuclear medicine physician at the Université De Rennes 1/CRLCC Eugène Marquis in Rennes, France, said in a written statement to OncLive^®.

Previously, the phase 2, randomized, open-label DOSISPHERE-01 trial (NCT02582034) conducted in France showed that patients with HCC who received personalized dosimetry with Y-90 glass microspheres (n = 28) experienced a significant improvement in objective response rate vs standard dosimetry (n = 28); rates were 71% (95% CI, 51%-87%) vs 36% (95% CI, 19%-56%), respectively (P = .0074).²

Garin detailed how the PROACTIF study was conducted and how Y-90 Glass Microspheres could fill an unmet need for patients with HCC in the interview.

OncLive: What was the rationale for conducting this research?

Garin: Reimbursement [for Y-90 Glass Microspheres] was initially obtained in France for a 5-year period. To continue to be eligible for reimbursement, French authorities required Boston Scientific to conduct this multicenter, real-word study with OS and quality of life as primary end points.

The study included 873 patients from 32 sites over 5 years. Data monitoring was conducted by Boston Scientific. The use of personalized dosimetry was recommended, and all centers were trained to personalize dosimetry in the same Center of Excellence—Rennes.

What were the key findings from the PROACTIF study?

This was the largest prospective, multi-center, post-approval, real-world study of the use of Y-90 to treat [patients with] primary liver cancer. The number of patients with primary liver cancer included in this study was twice the number of patients with primary liver cancer included in the European CIRSE [Cardiovascular and Interventional Radiological Society of Europe] registry with Y-90 resin microspheres.

The outcomes of the analysis demonstrate a median OS of 21.1 months in patients with intermediate and advanced HCC who were treated with TheraSphere, and a safety profile that is in line with historical studies of TheraSphere.

What do you want colleagues to take away from this research?

I want colleagues to take away the quality of data collected, the large patient population, and prolonged OS. [Also], the fact that this large, prospective, multi-center real-world study confirms the results of the DOSISPHERE-01 study. Large-scale randomized clinical trial data and registries continue to answer critical scientific questions, but access to data such as that used in the PROACTIF study has the potential to better inform and accelerate clinical decision-making and improve patient care.

What is most important for oncologists to know about TheraSphere Y-90 Glass Microspheres?

TheraSphere treatment is commonly referred to as selective internal radiation therapy and is comprised of millions of glass microspheres containing radioactive Y-90 delivered to liver tumors via catheter, which minimizes exposure to surrounding healthy tissue. PROACTIF is the largest, prospective, multicenter, post-approval, real-world study of the use of Y-90 to treat [patients with] primary liver cancer. [PROACTIF] demonstrated prolonged OS for [patients with] locally advanced HCC [with] BCLC [Barcelona Clinic Liver Cancer] stage B [disease] with large lesion[s] or BCLC stage C [disease] with portal vein thrombosis. This data set adds to the growing body of evidence that supports the use of TheraSphere for patients with HCC.

How could Y-90 Glass Microspheres fill an unmet need for patients with HCC? What unmet needs remain for this patient population?

Treatment of large primary liver cancer is challenging as treatment response decreases when tumor size increases, even with immuno-oncology [(IO) agents]. TheraSphere Y-90 Glass Microspheres and personalized dosimetry is effective in treating large lesions. For patients with portal vein thrombosis without extrahepatic spread, usually treated with IO therapy with palliative intent, TheraSphere Y-90 Glass Microspheres and personalized dosimetry allows for a curative strategy as some patients become candidates for surgery after effective treatment.

References

1. Garin E, Bailly C, Letang A, et al. The PROACTIF French registry study of Y-90 Glass Microspheres for the treatment of liver malignancies: interim analysis of 670 hepatocellular carcinoma (HCC) patients. J Vasc Interv Radiol. 2024;35(3):S113. doi:10.1016/j.jvir.2023.12.295
2. Garin E, Tselikas L, Guiu B, et al; DOSISPHERE-01 Study Group. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol. 2021;6(1):17-29. doi:10.1016/S2468-1253(20)30290-9