esmo.org

INTERMEDIATE HEPATOCELLULAR CARCINOMA MANAGEMENT

GI Preceptorship Nov 2018

Dr Choo Su Pin

Senior Consultant and Deputy Head, Medical Oncology

Co-Chair , Comprehensive Liver Cancer Centre

National Cancer Centre Singapore

2

Disclosures

� Advisory role and honoraria: Bayer, Sirtex, Bristol-Myers Squibb, Shire, Eisai, Ipsen, Norvatis, Celgene

� Speaker fees: Lilly Oncology, Sirtex. BMS

� Research funding: BMS, Sirtex

3

HBV is leading cause of HCC in Asia and China• 594 Mio cases in Asia2

HCV and life style is the leading cause of HCC in western population• 96 Mio cases in Nothern America and Europe

• 6th most common form of cancer worldwide more prominent in male

• Around 50% of HCC are diagnosed at advanced stage globally

Liver cancer is a common and deadly disease

1. Gravitz L, Nature 2014:516(7529):S1. 2. GloboCan 2012 http://globocan.iarc.fr/. 3. US National Cancer Institute Surveillance, Epidemiology, and End Results Program. 4. Ahmed, F. et al. Prev. Chronic Dis. 2008; 5:A74. 5. Scudellari N. Nature 2014; 2014:516(7529):S4; 6.Nature Outlook 12/14.

554000

228000

782,000 global new cases of liver cancer in 2012

Men Women

Very common Exceptionally lethal Heterogeneous Diseas e

• Second only to lung cancer in terms of mortality2,3

• Only 20% of diagnosed UK patients live longer than a year after diagnosis1

• Liver Cancer mortality in the US is growing at a higher rate than other cancers

Before 2017: estimated median survival for advanced HCC <

12 months

4

BCLC staging and treatment outcomes

Median OS 20 m Median OS 6.5 to 10.7m

5

ESMO

guidelines

6

The problem with intermediate HCC

� High heterogeneity� Clinical decisions differ from centre to centre coz of lack of clear

scientific evidence for many therapies� Thus, there are treatment discrepancies between guidelines

LOCOREGIONAL THERAPIES FOR INTERMEDIATE HCC:- NOT AMENABLE TO RESECTION/ TRANSPLANT OR ABLATION

- Transarterial Chemoembolisation ( TACE )

- Selective Internal radiotherapy (SIRT)

- Sorafenib

TACE

• Is there survival benefit

• What are the factors that affect TACE

outcomes?

• What is the best method for TACE

• How often should we TACE / what is

deemed TACE failure ?

TAE/TACE vs Best Supportive Care:

2-year Survival

Random effects model (DerSimonian and Laird)Odds ratio (95% CI)Author, journal year

Overall

Heterogeneity p=0.14 Favours treatment Favours contro l

Patients

503

Lin, Gastroenterology 1998 63

GETCH, NEJM 1995 96

Bruix, Hepatology 1998 80

Pelletier, J Hepatol 1998 73

Lo, Hepatology 2002 79

Llovet, Lancet 2002 112z=–2.3p=0.017

Llovet JM, et al. Lancet. 2003;362:1907–17Der Simonian R, Laird N. Controlled Clin Trials. 1986;7:177–88

0.01 0.1 0.5 1 2 10 100

Meta-analysis of 7 RCTs showed survival

benefit with TACE, OR 0.53, RR35% Llovet et al Hepatology 2003

Overall survival in RCTs with TACE : TACE is

better than best supportive care

TACE: Long-term survival outcomes

P=0.002

Llovet JM, et al.1 Lo C-M, et al.2

HR: 0.47 [95% CI 0.25–0.91]P=0.025

Relative risk of death, 0.49; 95% CI, 0.29-0.81; P=0.006253

1. Llovet JM, et al. Lancet 2002;359:1734–9. 2. Lo C-M, et al. Hepatology 2002;35:1164–71.

━Chemoembolization (n = 40)

━Control (n = 35)

━Chemoembolization (n = 40)

━Control (n = 39)

Factors affecting TACE outcomes: Prognostic scores in patients undergoing TACE

HAP score ART Score ABCR score

Child-Pugh score/

Albumin-bilirubin

Albumin <35g/L Child-Pugh increase

following TACE : +1,

+2 points)

Child-Pugh increased

following TACE ( >2

points)

Bilirubin > 17mmol/L

Tumor stage Tumor diameter > 7vm BCLC stage (B,C)

AFP AFP> 400ng/dL AFP> 200ng/ml

AST AST> 25% from

baseline

Radiological response Lack of radiological

response

Presence of

radiological response

Hucke et al 2014; Adhoute

2015; Kadalayi 2013

13

Contraindications to TACE

Absolute contraindications� Thrombus in the main portal vein and portal vein ob struction (high risk liver failure)� Encephalopathy� Biliary obstruction� Child-Pugh C cirrhosis� Renal failure� Extensive tumour burden� TechnicalRelative contraindications include a variety of other factors including, but not limited to:� Bile duct occlusion or incompetent papilla� Reduced PS� Impaired liver function (CP B)� High risk oesophageal varices � Branch portal vein thrombosis

Vogel ESMO guidelines

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Complications of TACE

� Post-embolization syndrome (60 – 80%)� Ischaemic damage with consequent liver failure � Hepatic abscess, biliary duct injury, cholecystitis (2%)� Gastroduodenal ulceration (3-5%)� Renal dysfunction (2%)� Pulmonary and cerebral lipiodol embolization (rare but can be

fatal)� Mortality approx. 2-3%

15

Conventional TACE vs DCBeads TACE� PRECISION V Trial : Phase 2 randomised , Europe, n=200 � Arm 1: TACE with doxorubicin� Arm 2: DC Beads with doxorubicin (150mg)

� Up to 3 times at 0,2,4mths

� Primary endpoint was = RR at 6 monthsResults:

� Less liver toxicity (p<0.001) and less doxorubicin toxicity (p=0.0001)with DC Beads.

DC Bead cTACE

Response rate 52% 44% p not sig

Disease Control Rate

63% 52% p not sig

16

17

Courtesy

Dr Huang

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OPTIMIS: patients not indicated for TACE given TACE

M Peck-Radosavlijevic 2018

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OPTIMIS: Variation in Timing to TACE Unsuitability Across Regions

Median days (SD)

EU & CANADAn=148

ASIA* n=156

JAPANn=91

CHINAn=80

Totaln=475

Median time to TACE unsuitability

79.5 (n=20)

109.5(n=20)

127.0(n=17)

42.0(n=5)

92.0(n=62)

Mean (SD) time between 1st & 2nd TACE

84.7 (70.9)(n=87)

83.5 (61.3)(n=75)

118.2 (101.7)(n=51)

80.8 (61.9)(n=37)

90.6 (75.4)(n=250)

TACE to initiation of other treatment

161.8 (69.0)(n=13)

142.6 (96.6)(n=20)

155.7 (73.3)(n=11)

72.0(66.2)(n=7)

140.4 (82.9)(n=46)

Timing After Initial TACE Treatment

Data on file. Bayer HealthCare. Whippany, New Jersey.*Excludes Japan and China.

There is a need to initiate treatment sooner following TACE unsuitability

M Peck-Radosavlijevic 2018

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OPTIMIS: Liver Dysfunction Observed After TACE Treatment

Summary Deterioration

EUROPEN=148(100%)

ASIA* N=156 (100%)

CHINAN=80(100%)

JAPANN=91(100%)

TotalN=475(100%)

Any Parameter 38 (25.7%) 66 (42.3%) 28 (35.0%) 38 (41.8 %) 170 (35.8%)

Alanine Aminotransferase 13 (8.8%) 16 (10.3%) 7 (8.8%) 10 (11.0%) 46 (9.7%)

Albumin 20 (13.5%) 25 (16.0%) 16 (20.0%) 24 (26.4%) 85 ( 17.9%)

Aspartate Aminotransferase 17 (11.5%) 35 (22.4%) 14 (17 .5%) 15 (16.5%) 81 (17.1%)

Bilirubin 12 (8.1%) 26 (16.7%) 13 (16.3%) 2 (2.2%) 53 (1 1.2%)

Prothrombin INR 9 (6.1%) 18 (11.5%) 9 (11.3%) 11 (12.1% ) 47 (9.9%)

Worsening of Lab AE Grade Relevant to the Liver

• After TACE, changes in liver laboratory values are documented

• It is essential to preserve liver function in order to maximize the

treatment potential for systemic therapy

M Peck-Radosavlijevic 2018

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What is TACE failure?Proposed algorithm based on ART score

Raoul 2014

WILL ADDING SYSTEMIC THERAPY TO TACE IMPROVE OUTCOMES?

Median OS with TACE alone about 20

months

---At least 5 negative trials

Rationale for combining TACE with

sorafenib:

• TACE is not curative and

repeated TACE compromises

the liver function

• TACE recurrence is associated

with upregulation of VEGF and

angiogenesis which sorafenib

can inhibit.

BRISK-TA (TACE +/- brivanib)and ORIENTAL (TACE +/- orantinib) trials negative

COMPARISON OF TACE COMBINATION TRIALSPost-TACE

Phase 3 (n=458)

SPACE

Rand ph2 (n=307)

TACE-2

Phase 3 ( n=399)

TACTICS

Rand ph 2 ( n=156)

Sites Japan/Korea Global (excl Japan) UK ( terminated early) Japan only

CP score A A A A to B7

Inclusion criteria <7cm; < 10 tumors

Responded toTACE

Unresectable Not for resection or

transplant

<10cm

< 10 tumors

TACE used cTACE, on demand DEB-TACE, at3,7 and

13m and then 6mthly

DEB-TACE ,on

demand

cTACE, on demand

Primary end point TTP 5.4m vs 3.7m,

HR 0.87, p=0.252

TTP 5.6 vs 5.5m

HR 0.797, p=0.072

PFS 7.8m vs 7.7m

HR 0.99, p=0.94

PFS 25.2m vs 13.5m

HR 0.59, p=0.006

Secondary endpoint OS 29.7 m, HR1.06

p=0.79

OS not reached,

HR 0.898 , p =0.295

OS 21.1m vs 19.7m

HR0.97, p=0.57

Not reached yet

Definition of PD RECICL2014 mRECIST RECIST1.1 unTACE-able

progression

Sorafenib duration 17 weeks 21 weeks 17.1 weeks 38.7 weeks

Adapted from Kudo, Oncology 2017

Slides courtesy of: Masatoshi Kudo, MD, PhD

Study Schema

Inclusion criteria

・Unresectable HCC

・Child-Pugh score;<7

・Prior TACE; 0-2

・Viable tumor

(<10 nodules , <10cm)

・Adequate organ function

Exclusion criteria

・EHS/MVI

TACESorafenib

(400mg od→400㎎ bid)

UnTACEable progression/

Progression to TACE failure

Ran

do

miz

atio

n (

1:1)

Co-Primary Endpoint

PFS/OS (Gatekeeping strategy)

Secondary Endpoint

TTUP, TTP, ORR

Safety

n=156

• Sorafenib 400mg daily was started 2-3 weeks before 1st TACE to check the tolerability and

to block the VEGF receptors after TACE followed by 800mg daily

• Sorafenib was interrupted 2days before and 3 days after each TACE session as long as

organ function is maintained within TACE re-starting criteria

• Repeated TACE is recommended on demand when viable lesion is more than 50%

compared with baseline tumor volume or in the investigator’s discretion

• Radiological assessment was done every 8 weeks by investigators

Sorafenib arm (n=80)

Control arm (n=76)

Stratification: sites, within Milan, No of prior TACE

4. TACTICS trial

Presented by: Masatoshi Kudo, MD, PhD

Definition of Progression Free Survival (PFS)

Time from the randomization day to the following events:

1. Progression:� Untreatable (UnTACEable) progression

(Defined as inability of a patient to further receive or benefit from TACE)

1) Intrahepatic tumor progression (25% growth, RECICL JSH 20091)*

2) Deterioration of liver function to Child-Pugh C

3) Appearance of extrahepatic spread

4) Appearance of major vascular invasion

(*Note: In this trial new lesion is not regarded as “Tumor progression” since it is not the

treatment failure nor suggesting next line of treatment)

� Progression that meets the TACE failure/refractoriness criteria by JSH definition2

2. Any cause of death

1Kudo M, et al, Hepatol Res. 2010;40:686-692. 2Kudo M, et al. Dig Dis 2011;29:339-364RECICL: Response Evaluation Criteria In Cancer of the Liver JSH: Japan Society of Hepatology

Presented by: Masatoshi Kudo, MD, PhD

Definition of TACE failure/refractoriness (JSH Criteria)1

Intrahepatic lesion

i. Two or more consecutive insufficient responses of the treated tumor (viable

lesion >50%) even after changing the chemotherapeutic agents and/or reanalysis

of the feeding artery seen on response evaluation CT/MRI at 1–3 months after

having adequately performed selective TACE

ii. Two or more consecutive progressions in the liver (tumor number increases as

compared to tumor number before the previous TACE procedure) even after having

changed the chemotherapeutic agents and/or reanalysis of the feeding artery seen

on response evaluation CT/MRI at 1–3 months after having adequately performed

selective TACE

1Kudo M, et al. TACE Failure criteria JSH guideline. Dig Dis 2011;29:339-364

Presented by: Masatoshi Kudo, MD, PhD

Main inclusion / exclusion criteria

• Patients aged 20 years or over

• Life expectancy more than 12 weeks

• Typical HCC by histology, cytology, or diagnostic imaging such as dynamic CT (MRI)

• Unresectable HCC: the maximum diameter ＜10 cm, and the maximum number ＜10

• No or 1-2 prior history of TACE therapy before enrollment (prior TACE must be >4 M before)

• ECOG Performance Status (PS) score of 0 or 1

• Child-Pugh score of 7 points or less

Main inclusion criteria

Main exclusion criteria

• Macrovascular invasion (MVI)

• Extrahepatic spread (EHS)

Baseline Patient Characteristics

Characteristics Category

TACE with

Sorafenib

(n=80)

TACE

alone

(n=76)

Median Age at enrollment (range) 72.0(36-85) 73.0(53-86)

Male, n (%) Male 63 (78.8) 55 (72.4)

Female 17 (21.2) 21 (27.6)

Performance status, n(%) 0 71 (88.8) 67 (88.2)

1 9 (11.3) 9 (11.8)

Etiology, n(%) Hepatitis B 10 (12.5) 2 (2.6)

Hepatitis C 38 (47.5) 53 (69.7)

Child-Pugh score , n(%) 5 64 (80.0) 54 (71.1)

6 15 (18.8) 17 (22.4)

7 1 (1.3) 5 (6.6)

AFP, n(%) <200 ng/mL 64 (80.0) 60 (78.9)

≥200 ng/mL 16 (20.0) 16 (21.1)

Characteristics Category

TACE with

Sorafenib

(n=80)

TACE

alone

(n=76)

Tumor burden, n(%) Within Milan 26 (32.5) 31 (40.8)

Over Milan 54 (67.5) 45 (59.2)

BCLC stage, n(%) A 25 (31.3) 30 (39.5)

B 46 (57.5) 37 (48.7)

C 9 (11.3) 9 (11.8)

Prior TACE, n(%) 0 45 (56.3) 48 (63.2)

1-2 35 (43.8) 28 (36.8)

Presented by: Masatoshi Kudo, MD, PhD

POSSIBLE REASONS WHY THESE TRIALS FAILED OR SUCCEEDEDPost-TACE SPACE TACE-2 TACTICS

Mean daily dose of

sorafenib was only

386mg/ day ( 73% dose

reductions and 91%

interruptions)

Three were significant

differences in TTP

between Korean and

Japan cohorts

- Korean patents had

longer duration of

treatment

- Japanese patients

had more lesions

and were more

elderly

Scheduled TACE- could this have

resulted in unnecessary

compromise of liver function or

inadequate TACE in some? E.g.

One-third of those in sorafenib arm

received only 1 x TACE

Asians had better HR than non-

Asians and were also on longer

duration of sorafenib (30 weeks vs

17.4 weeks) and more TACE

- More non-Asians had

unTACEable progression due to

liver function deterioration rather

than lack of response

As RECIST 1.1 used for

determining progression,

new intrahepatic lesionsin

non-TACEd areas were

considered PD

- Does this mean

treatment is not

working and do TACE

trials require a

different definition of

PD

- Should time to TACE

progression ( TTTP)

be used instead?

Different definition of PFS

–and what is considered

TTTP

Longer sorafenib

treatment duration (38.7

weeks) may be the key

of success of this trial

as compared with

previous failed trials

(Post TACE; 17.0 wks,

SPACE; 21.0 wks, TACE

2; 17.1 wks).

these trials suggest that the duration of sorafenib ( +/- TACE

duration) results in better outcomes

� What is optimal duration and frequency of TACE

� What is best method and chemotherapy for TACE

� Do the results of TACTICS apply to everyone else?

UNANSWERED QUESTIONS ABOUT TACE

SIRT (SELECTIVE INTERNAL RADIATION THERAPY)

• HCC is radio-sensitive• But external beam radiation risks significant collateral damage and

toxicity to liver.• However HCCs are almost

exclusively supplied by the artery – used to deliver local radiation therapy -

brachytherapy

Ytrium-90 tagged glass or resin

microspheres

–Yttrium-90: delivers radiation;

penetration avg 2.5 mm, max 11.0 mm

–Microsphere: delivers Yttrium-90 to

HCC

•Needs pretreatment technetium-00m

scan to ensure limited radiation

exposure to lung/GI tract

•Safe for those with branch portal vein

thrombosis

SIRT Selective Internal Radiotherapy

�

90Y microspheres in Patients with HCC and PVT

35

SIRT vs TACE

Zhang Y, 2015 Meta-analysis N=8 trials Better OS and TTP

with SIRT vs TACE

Salem R 2016 Randomised phase

2 trial

SIRT vs cTACE in

BCLC A and B HCC

TTP 26m vs 6.8 m

� No randomized phase 3 trials comparing both modalities

36

Slide 14

Presented By Edward Kim at 2018 Gastrointestinal Cancers Symposium

Courtesy

of E Kim

37

Slide 15

Presented By Edward Kim at 2018 Gastrointestinal Cancers Symposium

Courtesy

of E Kim

38

SARAH trial: a randomized controlled trial comparing efficacy and safety of SIRT (with yttrium -90 microspheres) and sorafenib in patients with locally advanced hepatoc ellular carcinoma

https://clinicaltrials.gov/ct2/show/NCT01482442

� 25 centres in France� Co-investigators: hepatologists, oncologists,

radiologists and nuclear medicine MDs

V. Vilgrain et al 2018

39

Study Design and Assessments

Presented By Pierce Chow at 2017 ASCO Annual Meeting

SIRveNIB trial: Phase II multi-centre, open label randomized controlled trial of SIRT versus

sorafenib in locally advanced HCC

40

SARAH vs SIRveNIB : trial endpoints and criteriaSARAH SIRveNIB

Primary Endpoint OS OS

Secondary endpoints Safety and tolerability

QOL

PFS at 6 months

Safety and tolerability

QOL

PFS at 6 months

Inclusion criteria Unresectable HCC

- BCLC C

- BCLC A/B if new lesions or unsuitable for

further radical therapy or no response after

TACEx2

- CP A to B7

- ECOG 0-1

- Fit for sorafenib or SIRT

Unresectable HCC with or without PVT

- BCLC B or C without extrahepatic

metastases

- CP A to B7

- ECOG 0-1

- Fit for sorafenib or SIRT

- Not more than 2 prior hepatic artery

directed therapies

- 26.6% did not get SIRT and 7.2% did not get

sorafenib

- 28.6% did get SIRT and 9% did not get

sorafenib

41

SARAH SIRveNIB

Sample size 467 360

Main PVT 32% 30%

Etiology Alcohol. 68%

HCV. 25%

NASH. 23%

HBV 51%

HCV 14.3%

Both HBV+HCV 2.2%

BCLC stage A/B/C 3.8/ 27.8/ 68.4% 0/ 54.9/ 44.5%

OS SIRT 8m vs sorafenib 9.9m

HR 1.15, p=0.18

SIRT 8.9m vs soraf 10m

HR1.12 , p=0.36

PFS/ TTP PFS 4.3 vs 3.7m

HR0.97, p=0.77

TTP 6.08 vs 5.36m

HR 0.88, p=0.287

ORR ( CR + PR) 19% vs 11.6%, p=0.042 16.5% vs 1.7% , p<0.0001

42

In SARAH: Better QOL with SIRT compared to sorafeni b In SIRveNIB: Better safety profile with SIRT

Intention-To-Treat populationN=459

SCREENING

1⁰ endpointNon-inferiority (1 st step) or superiority (2 nd step) of Primovist-MRI vs. CE-CT

MICRO-Tx SYSTEMIC Tx

Randomise

11:10

n = 375

sorafeni

b

SIR-

Spheres

sorafeni

b

Palliative Group

Local Ablation Group(<4 tumours; <5 cm each)

Randomise

1:1

n = 290

sorafeni

b

placebo

RFA

Contrast-

enhanced CT

Primovist®-

enhanced MRI

Off Study• BCLC 0• BCLC D

Time to Recurrence

Overall Survival

1⁰ endpoint

Assign to

study arm

Imaging Sub-Study

SORAMIC Trial: SchemaEuropean Trial

NEGATIVE trial

SIRT + sorafenib vs sorafenib: OS

12.1m vs 11.5m

44

ROLE of SIRT in ESMO guidelines

ESMO

guidelines

“SIRT is not recommended

as first-line therapy for

patients in intermediate or

advancedstage[I,E]

SORAFENIB IN INTERMEDIATE HCC

When TACE fails or not suitable for further locoregional therapy

Bruix J, et al. J Hepatol 2009; 50: S28–S29.

Lencioni R. ESMO-ECCO oncology meeting Stockholm; 2011.

avarone M, et al Hepatology 2011; 54(6): 2055–2063.

BCLC-B patients SHARP subgroup

analysis

GIDEON Italian SOFIA

Number of patients N=54 sorafenib

N=51 placebo

N=311 N=74

OS 14.5 m (+ 39%) 12.6m 20.6m

TTP 6.9m ( +113%)

Safety Similar to BCLC C

ESMO GUIDELINES FOR HCC

FUTURE FOR INTERMEDIATE HCC

- Combining locoregional therapy with newer TKIs or immuno-oncology

agents

- Starting systemic therapy earlier in the treatment algorithm with increasing

evidence of good outcomes with newer systemic therapies and limits of

TACE

NCT03143270 A Multicenter Pilot Study of Nivolumab With Drug

Eluting Bead Transarterial Chemoembolization in

Patients With Advanced Hepatocellular

Carcinoma

Cohort 1:TACE – nivolumab 2 weeks later

Cohort 2: nivolumab 4 weeks before TACE –then nivo

continued x 1 year (No dosing on TACE day)

Cohort 3: nivolumab 4 weeks before TACE –then nivo

continued x 1 year ( Dosing on TACE day)

USA

NCT02837029 Phase I/Ib Study of Nivolumab in Combination With

Therasphere (Yttrium-90) in Patients With

Advanced Hepatocellular Carcinoma

Therasphere – nivolumab 4 weeks later USA

NCT03099564 A Pilot Study of Pembrolizumab in Combination

With Y90 Radioembolization in Subjects With

Poor Prognosis Hepatocellular Carcinoma With

Preserved Liver Function

SIRspheres –pembrolizumab 1 week later USA

NCT03203304 Phase I Study of Stereotactic Body Radiotherapy

(SBRT) Followed by Nivolumab or Ipilimumab

With Nivolumab in Unresectable Hepatocellular

Carcinoma

40Gy – nivolumab or nivolumab + ipilumumab 2 weeks

later

USA

NCT02821754 A Pilot Study of Combined Immune Checkpoint

Inhibition in Combination With Ablative Therapies

in Subjects With Hepatocellular Carcinoma

(HCC) or Biliary Tract Carcinomas (BTC)

Tremelimumab + Durvalumab with RFA or TACe or

cryoablation

USA

NCT03316872 Pembrolizumab and Stereotactic Radiotherapy

Combined in Subjects With Advanced

Hepatocellular Carcinoma - A Phase II Study

Pembrlizumab – SBRT from day 2 Canada

48

A Phase II Open-Label, Single Centre, Non-Randomize d Trial Of Y90-Radioembolization In Combination With Nivolumab In Asian Patients With Hepatocellular Carcinoma: An interim analysis

� Main aims of study: � 1) To evaluate the efficacy of combining Y90 radioembolisation with

nivolumab2) To evaluated the safety and tolerability of combining Y90 radioembolisationwith nivolumab3) Exploratory studies to assess immune markers and response to therapy

Day 1:

Y90- radioembolisation

Day 21:

i.v nivolumab 240mg over 1 hour,

every 2 weeks

MAA hepatic

angiogram: Suitable

for Y90

Enrolled

into trial

Liver

biopsyLiver

biopsy

Y90 Radioembolization (RE) followed by IV Nivolumab

240mg flat dose over 30 minutes administered 21 days (± 3

days) after RE and every 2 weeks thereafter

N=40

In collaboration with Prof Evan Newell (SiGN) and Dr

Zhai Weiwei ( GIS)

Choo SP et al ; AASLD Nov 2018

SHOULD WE BE STARTING SYSTEMIC THERAPY EARLIER IN

INTERMEDIATE HCC?

Galle 2017

Potentail new

therapeutic options

as other therapies

prove to be more

efficacious

CONCLUSION

• TACE is still the standard of care for intermediate HCC with good liver function

• In patients with TACE failure, PVT or poorer liver function , systemic therapy

should be given

• While SIRT resulted in better ORR, it did not result in better OS compared to

sorafenib. Thus role of SIRT is largely for very selected patients who are not

suitable for TACE or sorafenib ( not everyone agrees with this)

• Treatment of intermediate HCC will evolve as results from combination trials

become available

THANK YOU

For fellows and junior consultants

interested in clinical research:

SSO-ACORD Trial Concept

Development Workshop

4th July 2019

- Look out for submission date for

1-page study proposals

- Check out Singapore Society of

Oncology website and facebook