THERASPHERE ™

Y-90 Glass Microspheres I DOSISPHERE-01 Trial

Level I randomised trial showed that unresectable HCC patients who receive a
personalised TheraSphere dose using multicompartment dosimetry had a median
OS of 26.6 months– a 16-month improvement compared to the control arm.
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

“Personalised dosimetry is safe and leads to a meaningful improvement in the objective response rate and overall
survival of patients with locally intermediate/advanced hepatocellular carcinoma [...] when compared with standard
dosimetry.”

STUDY OBJECTIVE
A randomised, 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) Personalised
STUDY
(PDA); DESIGN
defined as multi-compartment Y-90 distribution of absorbed dose within the perfused volume that accounts for preferential blood
dosimetry
flow into the tumor compared with normal parenchyma.

Multicentre, randomized (1:1), prospective, phase 2 study

STUDY DESIGN
ITT population: Personalised (PDA) n=31; Standard (SDA) n=29

Treatment Follow-Up Assessments (efficacy, safety)

93 patients screened 74 patients screened

Key Eligibility Pre-Treatment

Standard Dosimetry (mITT n=28):
• Unresectable HCC • Arteriogram Post-
Dosimetry goal: 120±20 Gy to the perfused lobe Treatment
• ≥ 1 tumor ≥ 7cm • 99mTc-MAA using SPECT/CT
• BCLC A, B or C R
Exclusion Criteria 1:1
• Hepatic reserve after
• LSF >30Gy
1st SIRT ≥30%
• Risk of GI exposure Personalised Dosimetry (mITT n=28): 4-6W 3M 6M 12M
• Written consent
• Poor tumor or PVT targeting Dosimetry goal: ≥ 205 Gy to the index lesion;
250-300 Gy if possible. Limit non-tumor tissue
dose to no more than 120 Gy with hepatic reserve ≥30%.

KEY RESULTS: PERSONALISED DOSIMETRY IMPROVED SURVIVAL

MEDIAN OVERALL SURVIVAL (ITT POPULATION)

16 Month
1.00

0.75
26.6 months (95% CI: 11.7-NR)
Survival probability

Survival Improvement
(personalised vs. standard dosimetry)
0.50

22.9Month
0.25
10.7 months
PDA (95% CI: 6-16.8)
SDA HR=0.421 (95% CI: 0.215-0.826); p=0.0096
0.00
Median Overall Survival for PVT patients
0 5 10 15 20 25 30 35 40
in personalised arm vs. 9.5
Follow-up (in months) months in standard arm

29 23 17 9 3 3 3 2 1
At Risk
31 29 21 16 14 10 6 2 0
THERASPHERE ™
Y-90 Glass Microspheres I DOSISPHERE-01 TRIAL

PERSONALISED DOSIMETRY IMPROVED RESPONSE

INDEX LESION RESPONSE RATE AT 3 MONTHS USING EASL IN THE MITT POPULATION
PRIMARY STUDY ENDPOINT
80 PDA (n=28) p=0.0074

71.4%
71.4
SDA (n=28)
Percentage of Patients

70
60
50.0
50
40 35.7
30 25.0
21.4
20 Objective Response Rate
10.7
10 (personalised vs. 35.7%
in standard dosimetry)
0
Complete Response Partial Response Objective Response Rate
Index Lesion Response (Investigator Assessment)

PERSONALISED DOSIMETRY DOWNSTAGED MORE PATIENTS TO SURGERY

PATIENTS SUCCESSFULLY DOWNSTAGED TO SURGERY

50 PDA (n=28) 50 PDA (n=18)

SDA (n=28) SDA (n=21)

44%
Percentage of Patients

Percentage of Patients

40 40

30 36% 30

20 20

10
4% 10

0%
0 0

Overall Patient Population PVT Patient Population

36% of patients in the personalised arm were 44% of PVT patients in the personalised arm were
downstaged vs. 4% in the standardised arm downstaged vs. 0% in the standardised arm

DOSISPHERE-01 EDITORIAL:

“The DOSISPHERE-01 Study challenges the evolving narrative that patients with advanced
hepatocellular carcinoma should have systemic therapy at the expense of locoregional therapy. […]
Personalised dosimetry (ie, reaching specific threshold radiation doses) is a natural evolution of
selective internal radiation therapy with ⁹⁰Y-labelled microspheres.”3

– Robert J Lewandowski, MD, Riad Salem, MD, DOSISPHERE Editorial, Lancet Gastroenterology & Hepatology

1. Reasons for censoring: received another anti-cancer treatment before M3 evaluation (n=2), no evaluation at M3 evaluation (n=1) (10.7%)
2. Reasons for censoring: early deaths (before M3) (n=2), no evaluation at M3 (n=1), start another anti-cancer treatment before M3 evaluation (n=1) (14.3%)
3. Lewandowski, Robert J, Salem, Riad. Radioembolisation with personalised dosimetry: improving outcomes for patients with advanced hepatocellular carcinoma. Lancet Gastroenterol Hepatol 2020; Published
Online: November 06, 2020 https://doi.org/10.1016/S2468-1253(20)30306-X
 THERASPHERE ™
Y-90 Glass Microspheres I DOSISPHERE-01 TRIAL

PATIENT DEMOGRAPHICS (mITT population)

Parameter PDA (n=28) SDA (n=28)

Male (%) 92.9 92.9

Child-Pugh Status (%) CP A5: 78.6 CP A6/B7: 21.4 CP A5: 78.6 CP A6/B7: 21.4
BCLC (%) BCLC B = 11 BCLC C = 89 BCLC B = 7 BCLC C = 93
Bilobar (%) 43 57
Mean Total Bilirubin (μM/L±SD) 14.0±6.4 14.3±6.4
PVT present (%) 64.3 75.0
PVT Location (%) Segmental 29.6 Main/Lobar 30/33 Segmental 32.1 Main/Lobar 32/43
Index lesion (mean, cm) 10.5±2.4 10.9±2.57

TREATMENT CHARACTERISTICS AND DOSIMETRY (mITT population)

Investigator Assessments PDA (n=28) SDA (n=28) P value
One treatment, n=26 One treatment, n=23
Number of Y-90 glass microspheres treatment ns (not significant)
Two treatments, n=2 Two treatments, n=5

Activity administered GBq (mean, min-max) 3.6 (2.4-4.8) 2.6 (2.2-3.0) 0.0049

AD* to perfused liver (Gy) Mean (±SD) 178.4±59.9 120.3±15.2 0.0001

% of patients with AD to perfused liver> 150 Gy 68 4 <0.0001

AD to index lesion (Gy) Mean (±SD) 331.1±131.5 221.3±139.4 0.0007

% of patients with AD to index lesion > 205 Gy 88 38 <0.0008

AD to perfused normal tissue (Gy) Mean (±SD) 92.8±30.1 64.5±36.6 0.007

*AD=absorbed dose

LIVER ADVERSE EVENTS (Grade ≥3) Related to Y-90*

PDA (n=35) SDA (n=21)

Patients with ≥ 1 AE 3 (8.6%) 3 (14.3%)
Death 1 (2.8%) 1 (4.7%)
Liver AEs 4 (11.4%) 5 (23.8%)
Ascites 1 1
Encephalopathy 0 0
GI hemorrhage 0 2
Bilirubin increase/jaundice 1 2
Hepatic failure 2 0

*patients allocated to either PDA or SDA based on treatment received (dose received) versus allocation by randomisation

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.

CAUTION: The law restricts these devices to sale by or on the order of a physician. Indications, contraindications, warnings, and instructions for use can be found in the product labelling supplied with each device or at www.IFU-BSCI.com. Products shown for
INFORMATION purposes only and may not be approved or for sale in certain countries. This material not intended for use in France.

Results from case studies are not necessarily predictive of results in other cases. Results in other cases may vary.
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or its affiliates. All rights reserved.
Note: Dose to the liver does not exceed 150 Gy. The physician should always take the above-noted Pre-treatment High Risk Factors into consideration for each patient when making decisions regarding the use of TheraSphere for treatment.
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. PI-931202-AB