SIR ABSTRACT 1

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• SIR ABSTRACT 1
• Safety, Response and Survival Outcomes of Y90
  Microsphere Radioembolization for Liver
  Metastases Results from a 151 Patient
  Investigational Device Exemption
  Multi-Institutional Study

• Study Chair
• Dr. Al Benson III, Northwestern Memorial
  Hospital
• Principle Investigators
• Dr. Gary Siskin, Albany Medical Center
• Dr. Jeff Geschwind, Johns Hopkins University
  Hospital
• Dr. Gregory Wiseman, Mayo Clinic Rochester
• Dr. William Rilling, Medical College of Wisconsin
• Dr. Mary Mulcahy, Dr. Riad Salem, Northwestern
  Memorial Hospital

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TheraSphere

• Y-90 integral constituent of the insoluble,
  biocompatible glass microspheres
• Mean sphere diameter 20-30 ?m
• 22,000 to 73,000 spheres / mg
• 6 dose sizes (3, 5, 7, 10, 15, 20 GBq)
• Dose by selected target volume
• Activity Desired Dose (Gy) Mass of Liver
  Target (kg)
• 50
• Arterial administration preferentially delivers
  microspheres to tumor spares normal parenchyma

Comparison of a Human Hair with TheraSphere?
(500x)
TheraSphere Y-90 Glass microspheres Radiation
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Study Overview

• Design
• Single-arm prospective, open-label
• Investigational Device Exemption (Nordion)
• Independent contract research organization
• Patients with Liver Metastases
• Primary Colorectal Cancer (CRC)
• Neuroendocrine (NE)
• Non-Colorectal/Non-Neuroendocrine
  (Non-CRC/Non-NE)
• Objectives
• Evaluate safety of TheraSphere at doses of 120
  10 Gy
• Evaluate Imaging Outcomes (RECIST v1.0)
• Response Rate (RR)
• Progression Free Survival (PFS)
• Independent central review
• Evaluate Overall Survival (OS)

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Main Inclusion Criteria

• 18 years of age
• Metastatic disease refractory to, or
  inappropriate for other systemic or
  liver-directed therapies
• Unresectable tumors
• Measurable disease
• Tumor replacement ? 50 by liver volume
• ECOG PS 0-2
• 30 day from prior cancer therapy
• Signed informed consent

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Main Exclusion Criteria

• Risk of hepatic or renal failure
• Serum creatinine gt2.0 mg/dL, unless on dialysis
• Serum bilirubin ? 2.0 mg/dL
• Albumin lt 2.0 g/dL
• History of hepatic encephalopathy
• Pulmonary insufficiency, clinically evident COPD
• Contraindication to TheraSphere or radiology
  procedures
• Cirrhosis or portal hypertension
• Prior Y90 microspheres or EBRT to the liver
• Intervention for, or compromise of the Ampulla of
  Vater
• Clinically evident ascites
• Co-morbidities or unresolved adverse events
• Positive serum pregnancy test

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Trial Treatment Schedule

• Pre-Treatment Procedures (lt 28 days prior to Day
  0)
• Screening for eligibility, informed consent
  medical history labs CT/MRI 99TcMAA scan and
  hepatic angiography (coil embolization)
• Develop treatment plan determine target volume
  activity to treat target volume account for
  decay schedule treatment, order dose vial
• Day 0 - Treatment first lobe position catheter,
  infuse microspheres
• Week 2 Telephone follow-up (safety)
• Week 5 Assess safety response, treat 2nd lobe
• Months 3, 6, 9, 12 then every 6 months Assess
  safety progression

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Study Enrollment

• First patient enrolled January 2007
• Last patient enrolled October 2009
• Last patient visit by March 1, 2011

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Results Patient Population

• Mean age 63.7 years
• 55.6 male
• 91.4 Caucasian
• 95.4 ECOG 0-1
• 68.9 bilobar disease
• Mean 2.5 years from initial diagnosis
• Medical history consistent with age/disease
• gt 50 patients with histories in GI,
  Musculoskeletal, General Cardiac, Dermatology,
  Allergy/immunology Endocrine body systems
• Non CRC/Non NE included cholangiocarcinoma,
  breast, ovarian, renal cell/bladder,
  esophageal/gastric, lung, pancreas

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Results Prior Treatments
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Results Dosing

• 243 lobar treatments per protocol
• Average 1.6 treatments per patient
• All patients received 120 Gy / 20
• No USNRC reportable medical events
• Median cumulative lung exposure lt10 Gy
• 2 of patients received gt 30 Gy to lung without
  clinical sequelae

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Results Total Liver Dosing (Gy)
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Study Analysis Populations

• Safety and OS populations
• all patients receiving TheraSphere (N 151)
• RR (CRPRSD)
• patients with completed independent image review
  (N 130)
• PFS populations
• CRC patients (N 56), NE patients (N 31)
  with complete independent image review

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Response by RECIST v1.0
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Survival Estimates

• CRC
• Median PFS 2.8 months 95 CI 1.2 - 3.1
• Median OS 9.4 months 95 CI 6.6 - 11.9
• Neuroendocrine
• Median PFS 14.6 months 95 CI 9.0 - 18.4
• Median OS 24.0 months 95 CI 17.5 - 36.3

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Kaplan-Meier Progression-Free Survival
MONTHS
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Kaplan-Meier Overall Survival
K-M Estimate of Survival Probability
MONTHS
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Conclusions

• TheraSphere demonstrated excellent tolerability
  and safety profile in patients with advanced
  metastatic liver disease
• Highly reliable delivery of planned radiation
  dose
• Prospective, multicenter confirmation of
  anti-tumor effect in patients without alternative
  therapeutic options
• Results were reproducible among all centers set
  the stage for international, multicenter phase 3
  RCTs