TheraSphere™ Y-90 Glass Microspheres

DOSISPHERE-01 trial

DOSISPHERE-01 overview

Level 1 evidence showed that unresectable HCC patients who received a personalized TheraSphere dose using multi-compartment dosimetry and were downstaged to resection saw durable, long-term overall survival.

Garin E, Tselikas L, Guiu B et al. Personalized 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: 17-29.

Garin E, Tselikas L, Guiu B, et al. Long-Term Overall Survival After Selective Internal Radiation Therapy for Locally Advanced Hepatocellular Carcinomas: Updated Analysis of DOSISPHERE-01 Trial. J Nucl Med. 2024;65(2):264-269. Published 2024 Feb 1. doi:10.2967/jnumed.123.266211

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Study objective

A randomized, multicenter, investigator sponsored phase II trial comparing the clinical outcomes of SIRT with TheraSphere in patients with intermediate/advanced HCC using two pre-treatment dosimetry determination methods: (1) Standard, single-compartment dosimetry (SDA); defined as a uniform distribution of absorbed dose within the perfused volume – both tumor and normal liver or (2) Personalized dosimetry (PDA); defined as multi-compartment Y-90 distribution of absorbed dose within the perfused volume that accounts for preferential blood f low into the tumor compared with normal parenchyma.

Study design

Process chart with 93 patients screened, 74 patients screened, treatment and follow-up assessments (efficacy, safety).

Key results

After analysis of long-term 65.8 month follow-up, improvement in median OS was sustained in the PDA group.

Median overall survival (global mITT population)

Chart showing 16 month survival improvement (personalized vs. standard dosimetry) and 22.9 month overall survival for PVT patients in personalized arm vs. 9.5 months in standard arm.

Cheng AL, Qin S, Ikeda M, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022;76:862–873.
Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1:1–12.

* TheraSphere not indicated for patients with PVT.

** IMbrave150 patient characteristics = unresectable HCC, Child-Pugh A, ECOG 0 or 1. Exclusion criteria was history of autoimmune disease, coinfection with hepatitis B & C viruses, and untreated or incompletely treated esophageal or gastric varices with bleeding or high risk of bleeding. STRIDE patient characteristics = unresectable HCC, BCLC B or C, Child-Pugh A, ECOG 0 or 1, & at least 1 measurable lesion per RECIST v1.1. Exclusion criteria was meaningful ascites, main PVT, or coinfection with hepatitis B & C viruses.

Personalized dosimetry allowed more patients to be downstaged to resection, resulting in durable, long-term overall survival

Patients successfully downstaged to surgery

Chart showing 36% of patients in the personalized arm were downstaged vs. 4% in the standardized arm.

36% of patients in the personalized arm were downstaged vs. 4% in the standardized arm

Chart showing 44% of PVT patients in the personalized arm were downstaged vs. 0% in the standardized arm.

44% of PVT* patients in the personalized arm were downstaged vs. 0% in the standardized arm

Median overall survival

(secondary resection status)

Median overall survival

(global mITT population censored at time of surgery)

The prognostic impact of secondary surgery on long-term OS is highlighted by the loss of difference in median OS censored at the time of surgery between arms.

Significantly improved response rate with personalized dosimetry

Index lesion response rate at 3 months using EASL in the mITT population

Chart showing Primary Study Endpoint of 71.4% Objective Response Rate (personalized vs. 35.7% in standard dosimetry).

* TheraSphere not indicated for patients with PVT.

OS rates decreased for patients with poor features (those randomly assigned to SDA, receiving a TD <205 Gy or a PLD <150 Gy, or not downstaged to resection). Only resected patients displayed an OS rate >50% at 5 years.

OS rates from 2 to 5 years (mITT population)

various parameters at 2 years, 3 years and 5 years

*TheraSphere not indicated for patients with PVT

Data in parenthesis are 95% CIs.

Patient demographics (mITT population)

patient parameters for 28 PDA and 28 SDA patients.

*TheraSphere not indicated for patients with PVT

Data in parenthesis are 95% CIs.

Treatment characteristics and dosimetry (mITT population)

investigator assessment for 28 PDA and 28 SDA patients.

*AD=absorbed dose.

Liver adverse events (Grade ≥3) Related to Y-90**

adverse liver events for 35 PDA and 21 SDA patients.

** Patients allocated to either PDA or SDA based on treatment received (dose received) versus allocation by randomization.

Conclusion

After a long-term follow-up period, a meaningful improvement in OS was sustained after personalized dosimetry. OS was dramatically improved for patients who were downstaged toward resection and then resected, including most PVT* patients. Because the 5 year survival rates for patients without resection remain low, randomized trials comparing SIRT with personalized dosimetry plus immunotherapy versus immunotherapy alone are now warranted in this specific patient population.

Boston Scientific is not responsible for the collection, analysis or reporting of the investigator-sponsored research output which is the sole responsibility of the investigators. Boston Scientific’s involvement in investigator-sponsored research is limited to providing financial support for research that advances medical and scientific knowledge about our products. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.

TheraSphere indications, safety, and warnings

TheraSphere is a registered trademark of Theragenics Corporation used under license by Boston Scientific Medical Device Limited, a wholly owned indirect subsidiary of Boston Scientific Corporation.