- The addition of selective internal radiation therapy (SIRT) to sorafenib (SOR) did not significantly improve overall survival compared to SOR alone in patients with advanced hepatocellular carcinoma based on two randomized controlled trials. - Subgroup analyses found potential clinical benefits for younger patients, those with non-alcoholic disease etiology, and those without cirrhosis. - Regorafenib, a multi-kinase inhibitor, significantly improved progression-free survival, overall survival, and disease control compared to placebo in patients with hepatocellular carcinoma progressing on sorafenib. - Lenvatinib, an oral multi-kinase inhibitor, demonstrated non-inferior

16. ITT population
SOR+SIRT
(n=216)
SOR
(n=208)
Median OS, months
(95% CI)
12.1
(10.6, 14.6)
11.5
(9.8, 13.8)
HR 1.0067 (0.82,1.25)
p=0.951
Conclusions:
• Addition of SIRT to SOR did not result in a significant improvement in OS vs. SOR alone
• Subgroup analyses (hypothesis generating) suggest a potential clinical benefit for younger patients, and
patients presenting with non-alcoholic aetiology, or without cirrhosis
OS in the PP population (N=288)
PP population
subgroup analysis*
SOR+SIRT vs. SOR
HR p-value
≤65 years 0.65 0.05
Non-alcoholic aetiology 0.63 0.012
Without cirrhosis 0.46 0.02
0
0.0
0.4
0.6
0.8
1.0
12
Months
Survivalprobability
62
0.2
Number at risk:
24
20
36
5
48
1
60
0114
75 23 8 2 0174
SOR+SIRT
SOR
Censored
PP
population
SOR+SIRT
(n=114)
SOR
(n=174)
Median OS,
months
(95% CI)
14.07
(10.9, 16.4)
11.14
(9.7, 13.9)
HR 0.86 (0.67,1.11)
p=0.253

17. Liver Embolotherapy Techniques
Kishore S, et al. Curr Oncol Rep. 2017;19:40.
Technique Mechanism Pros Cons
TAE
Induction of ischemic
necrosis at arteriolar level
using permanent embolic
(eg, small particles)
 Low cost, no chemotherapy adverse
events
 Postembolization syndrome;
may cause PEs
Conventional TACE
(cTACE)
Intrahepatic chemotherapy
combined with embolization
from ethiodized oil
 Strongest evidence for benefit based on
RCT data
 Technical variation between
operators (cTACE)
 Systemic release of
chemotherapy (cTACE)
 Postembolization syndrome
DEB-TACE
Intrahepatic chemotherapy +
embolization with slow-
release drug-eluting beads
 More standardized than cTACE, lower
systemic release of chemotherapy
 More expensive than cTACE
 Postembolization syndrome
Radioembolization
Radiation necrosis from
beta-emitting Yttrium-90
microspheres
 May improve TTP
 Fewer sessions required
 No postembolization syndrome
 May be safer in adv disease with PVT
 Radiation segmentectomy may be
curative
 FLR hypertrophy from radiation
lobectomy can facilitate resection while
providing tumor control
 Cost: 2-3x more expensive
 Requires multidisciplinary
coordination
 Nontarget delivery can cause
severe ulceration
 Potential biliary toxicity
 Radiation-induced liver disease

18. Secondary
outcomes Median HR 95% CI p
TTP, months 5.3 vs. 3.5 0.67 0.53, 0.85 0.003
PFS, months 5.2 vs. 3.6 0.73 0.59, 0.91 0.01
TRR 60.6% vs. 47.3% 0.005
Conclusions:
• SOR + cTACE did not improve OS vs. SOR alone in
patients with advanced HCC
• SOR + cTACE significantly improved TTP, PFS, and
TRR, and a survival benefit was observed in the
patients who received SOR+cTACE ≥2 sessions
Safety outcomes Arm C Arm S
SAEs 33.3% 19.8%
Grade3+
AEs
in>10%
Increased ALT
Hyperbilirubinaemia
Ascites
Hand-foot skin reaction
20.3%
11.8%
11.8%
10.5%
3.6%
3.0%
4.2%
11.4%
• Advanced HCC
• Child–Pugh A–B7
• ECOG 0–2
• TACE refractory
Stratification by:
• mUICC stage
• Vascular invasion
• Child–Pugh score
• AFP
Randomization
SOR + cTACE
(n=169)
SOR
(n=169)
Endpoints
• Primary: OS
• Secondary: TTP, PFS, TRR, AEs
Subgroup analysis: survival benefit for the 46% of patients in
the SOR+cTACE arm who received ≥2 cTACE vs. SOR:
• 18.6 vs. 10.8 months; HR, 0.58; 95% CI, 0.40–0.82; p=0.006
Overall
survival
SOR+cTACE
(n=170)
SOR
(n=169)
Median OS,
months
(90% CI)
12.8
(11.5, 15)
10.8
(8.7, 12.7)
0.91 (0.687, 1.205)
p=0.2898
0
0.00
0.50
0.75
1.00
12
Months
Survivalprobability
46
0.25
Number at risk:
24
13
36
3
48
0
60
0153
44 12 3 1 0167
Arm C
Arm S
Censored

19. NCCN Guidelines. Hepatobiliary Cancers. v2.2019. Slide credit:
FDA Approved for HCC
Agent Key Trial NCCN Recommendation
Cabozantinib* CELESTIAL Child-Pugh class A only (category 1)†
Nivolumab* CheckMate-40 Child-Pugh class A or B7 (category 2A)
Pembrolizumab* KEYNOTE-224 Child-Pugh class A only (category 2B)
Sorafenib Child-Pugh class A or B7 (after first-line lenvatinib; category 2A)‡
Regorafenib* RESORCE Child-Pugh class A only (category 1)†
Not Yet Approved
Agent Key Trial NCCN Recommendation
Ramucirumab REACH-2 AFP ≥ 400 ng/mL only (category 1)†
*FDA indication for patients who have received previous treatment with sorafenib. †Data reflect use on/after sorafenib. ‡There are no data to define
optimal treatment for those who progress after lenvatinib, nor for the use of lenvatinib after sorafenib.

20. Pts with HCC with
documented
radiologic
progression on
sorafenib
(N = 573)
Until PD, unacceptable
toxicity, or withdrawal
Regorafenib 160 mg PO QD
Days 1-21 of 28-day cycle
+ BSC
(n = 379)
Placebo
Days 1-21 of 28-day cycle
+ BSC
(n = 194)
Bruix J, et al. Lancet. 2017;389:56-66.
Randomized 2:1
Stratified by geography (Asia vs other), macrovascular invasion, extrahepatic
disease, ECOG PS (0 vs 1), AFP (< 400 ng/mL vs ≥ 400 ng/mL)

21. Response, %
mRECIST RECIST 1.1
Regorafenib
(n = 379)
Placebo
(n = 194)
Regorafenib
(n = 379)
Placebo
(n = 194)
ORR
10.6 4.1 6.6 2.6
2-sided P = .01 1-sided P = .02 (1-sided)
DCR
65.2 36.1 65.7 34.5
2-sided P < .001 1-sided P < .0001
Bruix J, et al. Lancet. 2017;389:56-66.
Regorafenib
(n = 379)
Placebo
(n = 194)
Events, n (%) 233 (61) 140 (72)
Censored, n (%) 147 (39) 54 (28)
Median OS, mos
(95% CI)
10.6 (9.1-12.1) 7.8 (6.3-8.8)
(HR: 0.63; 95% CI: 0.50-0.79; 1-sided P < .0001)
Placebo
Regorafenib
Mos From Randomization
ProbabilityofSurvival(%)
100
80
60
40
20
0
330 3 6 12 15 18 21 24 27 309
Placebo
Regorafenib
Mos From Randomization
ProbabilityofPFS(%)
100
80
60
40
20
0
330 3 6 12 15 18 21 24 27 309
Regorafenib
(n = 379)
Placebo
(n = 194)
Events, n (%) 293 (77) 181 (93)
Censored, n (%) 86 (23) 13 (7)
Median PFS,
mos (95% CI)
3.1
(2.8-4.2)
1.5
(1.4-1.6)
(HR: 0.46; 95% CI: 0.37-0.56; 1-sided P < .0001)

22. • Absence of DAE60 with SOR predicted absence of HFS with REGO in 89.18% of cases
• 4/37 (10.8%) patients who had not developed DAE60 on SOR had HFS-REGO
(NPV 89.2%)
DAE60 and HFS-REGO were associated with longer survival from start of SOR and REGO, respectively
HFS-REGO YES (n=24)
Median 14 months
95% CI 7.390, 20.610
1.0
0.8
0.6
0.4
0.2
0.0
0.0 10 20 30 40 50 60
1.0
0.8
0.6
0.4
0.2
0.0
0 2 4 6 8 10 12 14
Survival (months) since start of REGOSurvival (months) since start of SOR
Accumulatedsurvival
Accumulatedsurvival
DAE60 YES (n=32)
Median 24 months
95% CI 20.064, 27.936
DAE60 NO (n=37)
Median 19 months
95% CI 14.478, 23.522
p=0.042
HR 2.425
95% CI 1.703, 5.480
HFS-REGO NO (n=45)
Median 8 months,
95% CI 5.545, 10.455
p=0.021

23. Finn RS, et al. ASCO 2014. Abstract TPS4153.
O
O
CI
H
N
H
N
N
H2N
O
O
VEGFR FGFR
Angiogenesis
X
T202/Y204
S235/S236
T389
T421/S424
RAS
RAF
MEK
ERK1/2
Lenvatinib
PI3K
AKT
mTOR
S6K
S6
P
P
P
P

24. Pts with unresectable HCC, no prior
systemic therapy, ≥ 1 measurable target
lesion, BCLC stage B/C, Child-Pugh A,
ECOG PS 0/1, and adequate organ function
(N = 954)
Lenvatinib
8 mg (BW < 60 kg) or 12 mg (BW ≥ 60 kg) QD
(n = 478)
Sorafenib
400 mg BID
(n = 476)
Cheng AL, et al. ASCO 2017. Abstract 4001.
Stratified by region (Asia-Pacific vs Western),
MVI and/or EHS (yes vs no), ECOG PS (0 vs
1), and BW (< vs ≥ 60 kg)
 Primary endpoint: OS
– Noninferiority margin 1.08; criteria
met if upper limit of 2-sided 95% CI
for HR < 1.08
 Secondary endpoints: PFS, TTP, ORR,
QoL, lenvatinib PK
 Other endpoints: DCR, CBR,
exploratory biomarker analysis

25. Cheng AL, et al. ASCO 2017. Abstract 4001. Reproduced with permission.
ProbabilityofOS
Mos
Pts at Risk, n
Median, mos (95% CI)
Lenvatinib: 13.6 (12.1−14.9)
Sorafenib: 12.3 (10.4−13.9)
1.0
0.8
0.6
0.4
0.2
0
HR: 0.92 (95% CI: 0.79-1.06)
0.9
0.7
0.5
0.3
0.1
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42
478
476
436
440
374
348
297
282
253
230
207
192
178
156
140
116
102
83
67
57
40
33
21
16
8
8
2
4
0
0

26. Cheng AL, et al. ASCO 2017. Abstract 4001. Reproduced with permission.
ProbabilityofPFS
Mos
Pts at Risk, n
1.0
0.8
0.6
0.4
0.2
0
0.9
0.7
0.5
0.3
0.1
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42
478
476
345
262
223
140
172
94
106
56
69
41
44
33
28
22
14
14
9
9
4
4
2
2
0
2
0
0
Median, mos (95% CI)
Lenvatinib: 7.4 (6.9−8.8)
Sorafenib: 3.7 (3.6−4.6)
HR: 0.66 (95% CI: 0.57-0.77)
Log-rank test: P < .00001

27. Greten TF, et al. Gut. 2015;64:842-848.

28. Greten TF, et al. Clin Cancer Res. 2013;19:6678-6685.
Tumor
ablation
Antibody
Dendritic
cells
Peptides
Cytokines
T-cell activation
and priming
CTL mediated lysis
T-cell
activation
T-cell
Enhanced
T-cell function
Foxp3+ Treg
MDSC
IL-10, TGF-β
Oncolytic
virus
Antibody
Cancer vaccines
Elimination of
suppressor cells
Blockade of
immunosuppressive
cytokines
Checkpoint
blockade
Cytokines (GM-CSF,
IL-2, IFN-γ, etc)
Tumor cell
death

29. El-Khoueiry AB, et al. Lancet. 2017;[Epub ahead of print].
Dose Escalation (n = 48)
3 + 3 design
Dose Expansion (n = 214)
3 mg/kg
Without
viral
hepatitis
0.1 mg/kg
(n = 1)
0.3 mg/kg
(n = 3)
1.0 mg/kg
(n = 3)
3.0 mg/kg
(n = 3)
10 mg/kg
(n = 13)
n = 6 n = 9 n = 10 n = 10 n = 13
HCV
infected
0.3 mg/kg
(n = 3)
1.0 mg/kg
(n = 4)
3.0 mg/kg
(n = 3)
HBV
infected
0.1 mg/kg
(n = 5)
0.3 mg/kg
(n = 3)
1.0 mg/kg
(n = 3)
3.0 mg/kg
(n = 4)
Sorafenib untreated or intolerant
(n = 56)
Sorafenib progressor
(n = 57)
HCV infected
(n = 50)
HBV infected
(n = 51)
Phase I/II

30. El-Khoueiry AB, et al. Lancet. 2017;[Epub ahead of print].
Sorafenib Untreated or Intolerant Without Viral Hepatitis
ChangeFromBaseline
inTargetLesionTumor
Burden(%)
100
75
50
25
0
-25
-50
-75
-100
Sorafenib Progressor Without Viral Hepatitis
ChangeFromBaseline
inTargetLesionTumor
Burden(%)
100
75
50
25
0
0 726048362412 66544230186
0 726048362412 66544230186
-25
-50
-75
-100
HCV Infected
100
75
50
25
0
-25
-50
-75
-100
100
75
50
25
0
0 726048362412 66544230186
0 726048362412 66544230186
-25
-50
-75
-100
HBV Infected
Wks on TreatmentWks on Treatment
First occurrence of new lesion
Off treatment
% change truncated to 100%
CR or PR
Slide credit: clinicaloptions.com

31. Outcome Uninfected
Untreated/intolerant (n
= 56)
Uninfected
Progressor
(n = 57)
HCV Infected
(n = 50)
HBV
Infected
(n = 51)
All Pts
(N = 214)
ORR, % 23 21 20 14 20
 CR 0 4 0 2 1
 PR 23 18 20 12 18
 SD 52 40 46 41 45
 PD 23 32 28 45 32
Median OS, mos NR 13.2 NR NR NR
OS at 6/9 mos, % 89/82 75/63 85/81 84/70 83/74
Median PFS, mos 5.4 4.0 4.0 4.0 4.0
El-Khoueiry AB, et al. Lancet. 2017;[Epub ahead of print].

32. Melero I, et al. ASCO GI 2017. Abstract 26.
PD-L1 < 1% PD-L1 ≥ 1%
ORR, n/N (%) 4/26 (15.4) 2/9 (22.2)
PD-L1 < 1% PD-L1 ≥ 1%
ORR, n/N (%) 17/99 (17.2) 8/25 (32.0)
Dose Escalation Dose Expansion
100
50
0
-50
-100
Pts
ChangeinTargetLesionSize
FromBaseline(%)
< 1%PD-L1: NA≥ 1% < 1%PD-L1: NA≥ 1%
Pts

33. Event, %
0.1 mg/kg (n = 6) 0.3 mg/kg (n = 9) 1 mg/kg (n = 10) 3 mg/kg (n = 10) 10 mg/kg (n = 13) All Pts (N = 48)
Any
Grade
Grade 3/4
Any
Grade
Grade 3/4
Any
Grade
Grade 3/4
Any
Grade
Grade 3/4
Any
Grade
Grade 3/4
Any
Grade
Grade 3/4
Serious TRAEs* 17 17 11 11 0 0 0 0 8 0 6 4
AEs leading to d/c 0 0 11 11 0 0 10 10 8 8 6 6
Pts with TRAE 67 33 89 33 80 50 90 20 85 0 83 25
TRAEs
 Rash
 Pruritus
 Diarrhea
 Anorexia
 Fatigue
 Asthenia
 Weight ↓
 Nausea
 Dry mouth
17
33
0
17
17
0
0
0
0
0
0
0
0
17
0
0
0
0
22
33
33
22
22
11
11
11
11
0
0
0
0
0
0
0
0
0
20
0
0
10
10
0
0
0
10
0
0
0
0
0
0
0
0
0
20
10
10
0
0
10
0
10
0
0
0
0
0
0
0
0
0
0
31
23
8
8
0
8
15
8
8
0
0
0
0
0
0
0
0
0
23
19
10
10
8
6
6
6
6
0
0
0
0
2
0
0
0
0
Laboratory TRAEs
 AST ↑
 ALT ↑
 Lipase ↑
 Amylase ↑
 Anemia
 Albumin ↓
 Hyponatremia
0
0
17
17
0
0
0
0
0
17
0
0
0
0
22
22
11
0
11
11
0
22
22
0
0
0
0
0
30
10
40
40
10
10
20
20
0
40
10
10
0
0
10
20
20
20
0
0
0
10
10
10
10
0
0
0
31
15
15
15
15
8
8
0
0
0
0
0
0
0
21
15
21
19
8
6
6
10
6
13
4
2
0
0
El-Khoueiry AB, et al. Lancet. 2017; [Epub ahead of print]
*No treatment-related deaths

34. Zhu. Lancet Oncol. 2018;19:940.
 Primary endpoint: ORR
 Secondary endpoints: DOR, disease control, TTP, PFS, OS,
safety/tolerability
Adults with advanced
HCC who had PD with or
intolerance to sorafenib,
Child-Pugh A, BCLC stage
B or C, ECOG PS 0/1, life
expectancy > 3 mos
(N = 104)
Pembrolizumab
200 mg Q3W
Treatment continued up to
35 cycles or until PD,
unacceptable toxicity,
patient withdrawal, or
investigator decision

35. 100
50
0
-50
-100
ChangeFromBaselineinSizeof
TargetLesions(%)
Study Cohort (n = 104) Uninfected (n = 57) Infected With
Hepatitis C Virus (n = 26)
Infected With
Hepatitis B Virus (n = 21)
Zhu. Lancet Oncol. 2018;19:940.

36. 1. Sangro B, et al. J Hepatol. 2013;59:81-88.
2. Duffy AG, et al. J Hepatol. 2017;66:545-551.
3. Sangro B, et al. ILCA 2016. Abstract O-019.
Treatment n BCLC
(A/B/C)
Therapy Line Responses Survival
Tremelimumab
15 mg Q3 mos[1] 21 3/6/12
Not amenable to
ablative therapies
3/17 PR
(DoR: 3.6, 9.2, 15.8
mos)
DCR: 76.4%
Median TTP:
6.48 mos
Median OS: 8.2
mos
Tremelimumab
10 mg Q28 days
+ ablation[2]
32 --/7/21
BCLC B
Progressed on
sorafenib
5/19 PR
DCR: 84.2%
TTP: 7.4 mos
OS: 12.3 mos
Nivolumab
3 mg/kg[3] 206 C
Sorafenib
naive/tolerant
Progressed on
sorafenib
ORR: 9%
68/174 (39%) with
decline
in tumor burden
6-mo OS: 69%

37. Adult patients with advanced HCC
who experienced PD after
sorafenib; may have received up to
two previous systemic regimens;
Child-Pugh class A; ECOG 0/1
(N = 707)
Cabozantinib 60 mg PO QD
(n = 470)
Placebo PO QD
(n = 237)
Abou-Alfa. NEJM. 2018;379:54.
Until loss of clinical
benefit or unacceptable
toxicity

38. Mos
420 3 6 9 12 15 21 24 27 30 33 36 3918
ProbabilityofOS
1.0
0.8
0.6
0.4
0.2
0.0
Cabozantinib
Placebo
Mos
240 3 6 9 12 15 2118
1.0
0.8
0.6
0.4
0.2
0.0
Cabozantinib
Placebo
ProbabilityofPFSAbou-Alfa. NEJM. 2018;379:54.
Median OS, Mos
Cabozantinib
Placebo
10.2
8.0
HR: 0.76 (95% CI: 0.63-0.92;
P = .005)
Median PFS, Mos
Cabozantinib
Placebo
5.2
1.9
HR: 0.44 (95% CI: 0.36-0.52;
P < .001)

39. Patients with advanced
HCC, AFP > 400 ng/mL,
BCLC stage B/C,
Child-Pugh class A, ECOG
0/1, prior sorafenib
(N = 292)
Treatment continued until
unacceptable toxicity or
withdrawal
Ramucirumab + BSC
8 mg/kg IV Q2W
(n = 197)
Placebo + BSC
Q2W
(n = 95)
1. Zhu. Lancet Oncol. 2019;20:282. 2. Zhu. Lancet Oncol. 2015;16:859.
 Primary endpoint: OS; secondary endpoints: PFS, ORR, time to radiographic progression, time to FHSI-8 score
decline, time to ECOG PS decline

40. Mos Since Randomization
0 3 6 9 12 15 18 21 24 27
OS(%)
100
80
60
40
20
0
Mos Since Randomization
0 3 6 9 12 15 18 21 24
PFS(%)
100
80
60
40
20
0
Median OS, Mos
Ramucirumab
Placebo
8.5
7.3
HR: 0.710 (95% CI: 0.531-0.949;
P = .0199)
Median PFS, Mos
Ramucirumab
Placebo
2.8
1.6
HR: 0.452 (95% CI: 0.339-0.603;
P < .0001)
Zhu. Lancet Oncol. 2019;20:282.

48. Gene Gallbladder EHCC IHC
KRAS 3-38 10-15 45-54
BRAF 0-33 0 0-22
EGFR 9-12 5-18 10-20
ERBB2/HER2 16 5 0
PI3K 4 0 9
Adapted from De Groen et al. NEJM; 341(18):1368-78, 1999 Hezel et al, JCO, 2010 28:3531-3540

49. Wang et al. JCO; 29:4627-4632, 2011

50. Gallbladder cancer:
Online prediction calculator estimating benefit of adjuvant
chemotherapy or chemoradiotherapy
http://skynet.ohsu.edu/nomograms.

51. Treatment arm Gem Gem + Cis
Number of patients n=206 n=204
Deaths n(%)
141
(68.5) 122 (59.8)
Median survival (mo) 8.3 11.7
Log rank p value 0.002
Hazard ratio (95% CI) 0.70 (0.54, 0.89)
GEMCITABINE WITH OR WITHOUT CISPLATIN IN ADVANCED OR METASTATIC
BILIARY CANCER
(UK ABC-02 TRIAL)

52. 1. Khan SA, et al. J Hepatol. 2012;56:848-854. 2. Office for National Statistics. 1999.
https://www.springer.com/gp/book/9780116210319. 3. Primrose JN , et al. ASCO 2017. Abstract 4006.

53. Primrose JN , et al. ASCO 2017. Abstract 4006.
 Primary endpoint: OS
 Secondary endpoints: RFS, toxicity, QoL, health economics
Capecitabine 1250 mg/m2 BID
Days 1-14 of 21-day cycle for 8 cycles
(n = 223)
Observation
(n = 224)
Histologically confirmed
biliary tract cancer*; radical
and macroscopically
complete surgery; ECOG
PS ≤ 2; no previous
chemotherapy or
radiotherapy for biliary
tract cancer
(N = 447)
Primary analysis
after minimum
2-yr follow-up
Resection
*Included: intrahepatic CC, hilar CC, muscle-invasive gallbladder cancer, and lower common bile duct CC
Excluded: pancreatic, ampullary, mucosal (T1a) gallbladder cancers; incomplete recovery from prior surgery
Stratified by surgical center,
R0 vs R1 resection, ECOG PS

54. Primrose JN , et al. ASCO 2017. Abstract 4006. Reproduced with permission.
ITT Population
Treatment Median OS, Mos
(95% CI)
HR (95% CI)
Capecitabine 51.1 (34.6-59.1) 0.81 (0.63-1.04)
P = .097Observation 36.4 (29.7-44.5)
Treatment Median OS, Mos
(95% CI)
HR (95% CI)
Capecitabine 52.7 (40.3-NR) 0.75 (0.58-0.97)
P = .028Observation 36.1 (29.6-44.2)
Per Protocol Population
> 80% pts followed-up for 36 mos
0
25
50
75
100
PtsAlive(%)
0 12 24 36 48 60
Mos Since Randomization
0
25
50
75
100
PtsAlive(%)
0 12 24 36 48 60
Mos Since Randomization

55. Primrose JN , et al. ASCO 2017. Abstract 4006. Reproduced with permission.
Treatment Median RFS, Mos
(95% CI)
HR (95% CI)
Capecitabine 24.6 (18.9-36.7) 0.76 (0.58-0.99)
P = .039Observation 17.6 (12.8-27.6)
Treatment Median RFS, Mos
(95% CI)
HR (95% CI)
Capecitabine 25.9 (19.8-46.3) 0.71 (0.54-0.92)
P = .011Observation 17.6 (12.0-23.8)
0
25
50
75
100
PtsRecurrenceFree(%)
0 12 24 36 48 60
Mos Since Randomization
0
25
50
75
100
0 12 24 36 48 60
ITT Population Per Protocol Population
PtsRecurrenceFree(%)
Mos Since Randomization

56. Gemcitabine 1000 mg/m2 IV
over 30 min D1 and D8
+ Capecitabine 750 mg/m2
PO BID x 14 days
X
4 cycles
Concurrent EBRT with
Capecitabine 665 mg/m2
BID x 7 days for 6 weeks
(45 Gy to regional
lymphatics, 54-59.4 Gy to the
tumor bed)

57. Overall Survival by Margin of Resection
0%
20%
40%
60%
80%
100%
0 12 24 36 48 60
Months After Registration
R0
R1
N
54
25
Deaths
27
14
2-Year
Estimate
67%
60%
2-year estimate of OS=65% OS not significantly different by margin status:
2-year OS 67% vs 60%

58. Gem/platinum x 4 months (6 cycles)
followed by
5-FU (or capecitabine)/RT
Gem/platinum
Patients with
EHCC or GB
CA

59. Primrose JN , et al. ASCO 2017. Abstract 4006.