Ghassan Abou-Alfa, MD, MBA, Robin K. (“Katie”) Kelley, MD, Professor Riccardo Lencioni, MD, FSIR, EBIR, and Amit Singal, MD, MS, prepared useful practice aids pertaining to HCC for this CME/MOC activity titled, "Composing Personalized HCC Treatment Strategies: Insights on Harmonizing Patient Care With a Multidisciplinary Ensemble." For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2kAyqO9. CME/MOC credit will be available until November 5, 2020.

1. HCC Treatment Options by BCLC Stage1
and Selected Ongoing Phase 3 Clinical Trials
Access the activity, “Composing Personalized HCC Treatment Strategies: Insights on Harmonizing Patient
Care With a Multidisciplinary Ensemble” at PeerView.com/XKX40.
PRACTICE AID
BCLC
StageResection
OLT
BSC
Resection
OLT, RFA, MWA,
TARE, TACE,
SBRT
TARE
Nivolumab (2L),
pembrolizumab (2L)
Sorafenib (1L), lenvatinib (1L),
regorafenib (2L), cabozantinib
(2L), ramucirumab when AFP
≥400 ng/mL (2L)
TACE
TARE
Downsize OLT
Level of evidence
Strong Moderate Weak
0
A
B
C
D
RFA/MWA

2. AFP: alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; BSC: best supportive care; FFLP: freedom from local progression; HCC: hepatocellular carcinoma; MWA: microwave ablation; OLT: orthotopic liver transplantation; OS: overall survival; PFS: progression-free survival; RFA:
radiofrequency ablation; RFS: recurrence-free survival; SBRT: stereotactic body radiation therapy; TACE: transarterial chemoembolization; TARE: transarterial radioembolization.
1. Marrero JA et al. Hepatology. 2018;68:723-750.
HCC Treatment Options by BCLC Stage1
and Selected Ongoing Phase 3 Clinical Trials
Access the activity, “Composing Personalized HCC Treatment Strategies: Insights on Harmonizing Patient
Care With a Multidisciplinary Ensemble” at PeerView.com/XKX40.
PRACTICE AID
Ongoing Trials of First-Line Systemic Therapy in Intermediate/Advanced HCC
Ongoing Trials in Resected or Locally Advanced HCC
• Residual or recurrent disease after
TACE
• Primary endpoint: FFLP
• Estimated N = 160
NCT02762266
SBRT TACEvs
• Patients with high risk of recurrence
after resection
• Primary endpoint: RFS
• Estimated N = 530
CheckMate -9DX
(NCT03383458)
• Locoregional not amenable to
curative therapy
• Primary endpoint: PFS
• Estimated N = 600
EMERALD-1
(NCT03778957)
Durvalumab
± bevacizumab
+ TACE
Placebo + TACEvs
• Complete radiological response after
surgical resection or local ablation
• Primary endpoints: RFS and OS
• Estimated N = 950
KEYNOTE-937
(NCT03867084)
Pembrolizumab
(adjuvant)
PlacebovsNivolumab Placebovs
• Primary endpoint: OS
• Estimated N = 1,310
HIMALAYA
(NCT03298451)
Durvalumab
± tremelimumab
Sorafenibvs
• Primary endpoint: OS
• Estimated N = 368
NCT01730937
• Primary endpoints: PFS and OS
• Estimated N = 480
IMbrave150
(NCT03434379)
Atezolizumab
+ bevacizumab
Sorafenibvs
• Primary endpoints: PFS and OS
• Estimated N = 740
COSMIC-312
(NCT03755791)
Cabozantinib
± atezolizumab
Sorafenibvs
SBRT
+ sorafenib
Sorafenibvs
• Primary endpoints: PFS and OS
• Estimated N = 750
LEAP-002
(NCT03713593)
Pembrolizumab
+ lenvatinib
Placebo
+ lenvatinib
vs
• Patients with high risk of recurrence
after resection
• Primary endpoint: RFS
• Estimated N = 888
EMERALD-2
(NCT03847428)
Durvalumab
± bevacizumab
Placebovs
• Primary endpoint: OS
• Estimated N = 1,084
CheckMate -9DW
(NCT04039607)
Nivolumab
+ ipilimumab
Sorafenib
or lenvatinib
vs

3. a
Phase 3 level of evidence for all listed agents. b
Real-world effectiveness data in extended populations, including in patients with Child–Pugh B cirrhosis, are available.
AE: adverse event; AFP: alpha-fetoprotein; ECOG: Eastern Cooperative Oncology Group; HCC: hepatocellular carcinoma; HFSR: hand-foot skin reaction; TKI: tyrosine kinase inhibitor.
1. Adapted from slides presented by Amit Singal, MD, MS. 2. Llovet JM et al. NEnglJMed. 2008;359:378-390. 3. Kudo M et al. Lancet. 2018;391:1163-1173. 4. Bruix J et al. Lancet. 2017 Jan 7;389:56-66. 5. Abou-Alfa GK et al. NEnglJMed. 2018 Jul 5;379:54-63. 6. Zhu AX et al.LancetOncol. 2019;20:282-296.
Considerations for Selecting
and Sequencing Targeted Therapy for HCC1,a
Access the activity, “Composing Personalized HCC Treatment Strategies: Insights on Harmonizing Patient
Care With a Multidisciplinary Ensemble” at PeerView.com/XKX40.
PRACTICE AID
Drug
• Child–Pugh A cirrhosis, ECOG 0-1,
unresectable HCC with no prior
systemic therapy
• Excluded patients with >50% liver
involvement, main portal vein tumor
thrombus, and bile duct invasion
• Non-inferior OS compared
with sorafenib
• Improved objective
responses and time to
progression compared
with sorafenib
Lenvatinib
• Orally once daily
• Can be taken
with or without
food
• Increased
hypertension,
proteinuria, and
anorexia
• Tolerated sorafenib but with
radiographic progression
• Improved OS
Regorafenib
• Orally daily for
3 weeks with a
1-week holiday
• Similar to AE
profiles of other
TKIs
• Improved survival
compared with placebob
• Child–Pugh A cirrhosis, ECOG 0-1,
unresectable HCC with no prior
systemic therapy
• Orally twice daily
• Should be
taken 1-2 hours
removed from
food
• Increased HFSR
• Intolerant to sorafenib or with
radiographic progression
• Could have received an additional
line of systemic therapy
• Improved OS
Cabozantinib
• Orally once
daily
• Similar to AE
profiles of other
TKIs
• Intolerant to sorafenib or with
radiographic progression
• Patients with AFP ≥400 ng/mL
• Improved OS
Ramucirumab
• IV infusion
every 2 weeks
• Well tolerated with
low rates of dose
reductions or
discontinuations
Sorafenib
Inclusion Criteria Efficacy AE Profile Dosing
First-LineSetting2,3
Second-LineSetting4-6