Transcript TheraSphere Phase II trial results SIR 2011

SIR ABSTRACT #1
Safety, Response and Survival Outcomes of Y90
Microsphere Radioembolization for Liver
Metastases: Results from a 151 Patient
Investigational Device Exemption MultiInstitutional Study
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Study Chair
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Principle Investigators
– Dr. Al Benson III, Northwestern Memorial Hospital
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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
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)
Comparison of a Human Hair
with TheraSphere (500x)
• 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
TheraSphere Y-90 Glass
microspheres Radiation
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
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Evaluate Overall Survival (OS)
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
Main Exclusion Criteria
• Risk of hepatic or renal failure
– Serum creatinine >2.0 mg/dL, unless on dialysis
– Serum bilirubin  2.0 mg/dL
– Albumin < 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
Trial Treatment Schedule
• Pre-Treatment Procedures (< 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
Study Enrollment
CRC
N=61
NE
N = 44
Non CRC / Non NE
N = 46
All Patients
N = 151
N (%)
N (%)
N (%)
N (%)
Albany Medical
Center
17 ( 27.9)
5 ( 11.4)
10 ( 21.7)
32 ( 21.2)
Johns Hopkins
12 ( 19.7)
11 ( 25.0)
4 ( 8.7)
27 ( 17.9)
Mayo Clinic
4 ( 6.6)
10 ( 22.7)
8 ( 17.4)
22 ( 14.6)
Medical
College
Wisconsin
8 ( 13.1)
8 ( 18.2)
6 ( 13.0)
22 ( 14.6)
Northwestern
University
20 ( 32.8)
10 ( 22.7)
18 ( 39.1)
48 ( 31.8)
Study Center
• First patient enrolled: January 2007
• Last patient enrolled: October 2009
• Last patient visit: by March 1, 2011
Results – Patient Population
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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:
– > 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
Results – Prior Treatments
CRC
N = 61
NE
N = 44
Non CRC/
Non-NE
N = 46
2 or fewer therapies
43%
93%
59%
62%
3 or more therapies
57 %
7%
41%
38%
Systemic Chemotherapy
100%
30%
70%
70%
Hormone Therapy
0%
50%
20%
20%
Other
30%
10%
20%
20%
Prior Therapy
All Patients
N = 151
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 <10 Gy
• 2% of patients received > 30 Gy to lung without
clinical sequelae
Results – Total Liver Dosing (Gy)
CRC
N = 61
NE
N = 44
Non CRC/ NonNE
N = 46
Mean (SD)
115.3 ( 7.62)
116.4 ( 7.79)
116.3 ( 7.11)
116.0 ( 7.48)
Median (IQR)
114.3 ( 11.4)
115.0 ( 9.3)
116.1 ( 9.0)
115.0 ( 10.3)
100, 134
103, 138
97, 133
97, 138
Min, Max
Mean
(SD)
Median
(IQR)
Min,
Max
All Patients
N = 151
Site 1
Site 2
Site 3
Site 4
Site 5
112.2 ( 5.93)
116.3 ( 5.39)
117.3 ( 5.48)
120.2 ( 8.39)
111.7 ( 5.92)
111.7 ( 7.1)
117.4 ( 6.7)
116.7 ( 8.3)
119.6 ( 11.1)
110.7 ( 7.9)
102, 124
105, 126
108, 126
97, 138
104, 130
Study Analysis Populations
• Safety and OS populations
• all patients receiving TheraSphere (N = 151)
• RR (CR+PR+SD)
• patients with completed independent image review
(N = 130)
• PFS populations
• CRC patients (N = 56), NE patients (N = 31) with
complete independent image review
1
2
3
4&5
Response by RECIST v1.0
CRC
N = 56
NE
N = 31
Non CRC/Non-NE
N = 43
All Patients
N = 130
n (%)
n (%)
n (%)
n (%)
CR
0 ( 0.0)
0 ( 0.0)
0 ( 0.0)
0 ( 0.0)
PR
5 ( 8.9)
4 ( 12.9)
3 ( 7.0)
12 ( 9.2)
SD
30 ( 53.6)
24 ( 77.4)
24 ( 55.8)
78 ( 60.0)
PD
21 ( 37.5)
3 ( 9.7)
16 ( 37.2)
40 ( 30.8)
CR + PR + SD
35 (62.5)
28 (90.3)
27 (62.8)
90 (69.2)
Response by
RECIST
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]
K-M Estimate of Hepatic or Extra-Hepatic PFS Probability
Kaplan-Meier Progression-Free Survival
MONTHS
K-M Estimate of Survival Probability
Kaplan-Meier Overall Survival
MONTHS
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