1. SIRveNIB: Randomized Phase III Trial of Selective Internal Radiation Therapy vs Sorafenib in Locally Advanced HCC
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
HCC, hepatocellular carcinoma.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. Management of Locally Advanced HCC
Most pts with HCC have locally advanced disease at diagnosis (± PVT)
Both SIRT and sorafenib have efficacy in this setting but through different mechanisms of action
SIRT: brachytherapy that delivers radiation to tumor bed via Y90 resin microspheres
Sorafenib: multikinase and angiogenesis inhibitor
Definitive trial comparing these 2 modalities needed to inform decision making
SIRveNIB: randomized, controlled, open-label phase III trial of SIRT vs sorafenib in locally advanced HCC not amenable to curative therapy
Current report detailed SIRveNIB findings
HCC, hepatocellular carcinoma; PVT, portal vein thrombosis; SIRT, selective internal radiation therapy.
Slide credit: clinicaloptions.com
Chow M, et al. ASCO Abstract 4002.

3. SIRveNIB: Study Design
Randomized, controlled, open-label phase III trial conducted at 27 centers in 11 countries in Asia-Pacific region
Stratified by site, portal vein thrombosis
Pts with locally advanced HCC* not amenable to curative therapy and without extrahepatic metastases (N = 360)
SIRT with Y90 resin microspheres 
(n = 182)
Followed Q3 mos until PD by central CT review and for survival
Sorafenib 400 mg BID 
(n = 178)
BCLC, Barcelona Clinic Liver Cancer; DCR, disease control rate; ECOG, Eastern Cooperative Oncology Group; HCC, hepatocellular carcinoma; PD, progressive disease; PS, performance status; PVT, portal vein thrombosis; RECIST, Response Evaluation Criteria in Solid Tumors; SIRT, selective internal radiation therapy; TTP, time to tumor progression; CT, computed tomography.
*Locally advanced HCC without extrahepatic metastases; PVT permitted; BCLC B and BCLC C without distant metastases; ECOG PS 0-1; Child–Pugh A-B (up to 7 points); life expectancy ≥ 3 mos; ≤ 2 prior administrations of hepatic artery-directed therapy
Primary endpoint: OS; secondary endpoints: ORR (RECIST 1.1), DCR, TTP, PFS, safety
Slide credit: clinicaloptions.com
Chow M, et al. ASCO Abstract 4002.

4. SIRveNIB: Baseline Characteristics
ITT Population
Treated Population
Characteristic
SIRT (n = 182)
Sorafenib (n = 178)
SIRT (n = 130)
Sorafenib (n = 162)
Mean age, yrs (SD)
59.5 (12.9)
57.7 (10.6)
60.9 (11.5)
57.5 (10.6)
Male, % 81 85 82
Mean BMI (SD)
23.2 (4.2)
24.0 (4.6)
23.2 (4.3)
24.1 (4.7)
Portal vein thrombosis, % 31 30 23
ECOG PS 0, % 74 79 78
Child–Pugh stage A, % 90 88
BCLC stage B, % 55 61 64 59
Tumor size > 50% of liver, % 24 18 22
Hepatitis, % B C
B and C 51 14 2 58 11 3 52 15 12 1
BCLC, Barcelona Clinic Liver Cancer; BMI, body mass index; ITT, intent to treat; SD, standard deviation; SIRT, selective internal radiation therapy.
Slide credit: clinicaloptions.com
Chow M, et al. ASCO Abstract 4002.

5. SIRveNIB: Treatment Exposure
SIRT (n = 130 treated)
52 pts (28.6%) did not receive allocated treatment
Median time from randomization to treatment: 21 days
Mean activity administered (single dose): 1.8 GBq
Sorafenib (n = 162 treated)
9% did not receive allocated treatment
Median time from randomization to start of treatment: 3 days
Mean daily dose: mg
Median treatment duration: wks
Proportion with ≥ 80% adherence to planned doses: 89%
SIRT, selective internal radiation therapy.
Slide credit: clinicaloptions.com
Chow M, et al. ASCO Abstract 4002.

6. SIRveNIB: OS in ITT and Treated Populations
OS results generally consistent across subgroups
OS ITT
OS Treated
1.0
SIRT (n = 182)
Sorafenib (n = 178)
Median OS, mos
8.84
10.02
HR: 1.12 (95% CI: ; P = .360)
1.0
SIRT (n = 130)
Sorafenib (n = 162)
Median OS, mos
11.27
10.41
HR: 0.86 (95% CI: ; P = .273)
0.8
0.8
0.6
0.6
SIRT
Sorafenib
SIRT
Sorafenib
Proportion of Pts Achieving OS
Proportion of Pts Achieving OS
0.4
0.4
0.2
DCR, disease control rate; ITT, intent to treat; SIRT, selective internal radiation therapy; TTP, time to tumor progression
0.2
0.0
0.0 6 12 18 24 30 36 6 12 18 24 30 36
Mos Since Randomization
Mos Since Randomization
Slide credit: clinicaloptions.com
Chow M, et al. ASCO Abstract Reproduced with permission.

7. SIRveNIB: Secondary Efficacy Outcomes
ITT Population
Treated Population
Efficacy Outcome
SIRT (n = 182)
Sorafenib (n = 178) HR
P Value
SIRT (n = 130)
Sorafenib (n = 162)
Median TTP, mos
Overall
In liver
6.08
6.11
5.36
5.39
.287
.241
6.41
6.77
5.45
0.73 --
.019
.013
Median PFS, mos
5.85
6.01
5.06
0.89
.306
.259
6.28
6.67
5.22
.009
ORR, %
16.5
1.7
< .001
23.1
1.9
DCR, %
41.8
42.7
.915
58.5
46.9
.059
DCR, disease control rate; ITT, intent to treat; SIRT, selective internal radiation therapy; TTP, time to tumor progression
Slide credit: clinicaloptions.com
Chow M, et al. ASCO Abstract 4002.

8. SIRveNIB: Safety Outcomes
60.0% (P < .001)
Pts who experienced at least 1 AE
84.6%
31.5% (P < .0001)
Pts who experienced at least 1 TRAE
74.7%
27.7% (P < .0001)
Pts who experienced at least 1 ≥ grade 3 AE
50.6%
13.1% (P < .0001)
Pts who experienced at least 1 ≥ grade 3 TRAE
37.7%
20.8% (P = .0091)
Pts who experienced at least 1 serious AE
35.2%
AE, adverse event; SIRT, selective internal radiation therapy; TRAE, treatment-related adverse event.
4.6% (P = .1715)
Pts who experienced at least 1 serious TRAE
9.3% 20 40 60 80
100
SIRT (N = 130)
Sorafenib (N = 162)
Pts (%)
Slide credit: clinicaloptions.com
Chow M, et al. ASCO Abstract Reproduced with permission.

9. SIRveNIB: Select Adverse Events
Grade 1/2
Grade 3-5
SIRT (n = 130)
Sorafenib (n = 162)
P Value
Constipation
5.6
.0051 --
Diarrhea
1.5
25.9
< .001
3.7
.0353
Fatigue
3.8
11.7
.0175
Alopecia
9.9
< .0001
PPE syndrome
0.8
38.3
16.7
Rash
11.1
Hypertension
13.6
1.2
.5043
PPE, palmar-plantar erythrodysesthesia.
All other events not significantly different between groups
Slide credit: clinicaloptions.com
Chow M, et al. ASCO Abstract 4002.

10. SIRveNIB: Investigator Conclusions
Study failed to meet primary endpoint
SIRT and sorafenib yielded similar OS in patients with locally advanced HCC not amenable to curative therapy
However, pts treated with SIRT vs sorafenib demonstrated
Significantly higher ORR
Fewer AEs and serious AEs
AE, adverse event; HCC, hepatocellular carcinoma; SIRT, selective internal radiation therapy.
Slide credit: clinicaloptions.com
Chow M, et al. ASCO Abstract 4002.

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