Prim. Univ. Prof. Dr. Markus Peck-Radosavljevic
Abteilung Innere Medizin & Gastroenterologie (IMuG)
Hepatologie, Endokrinologie, Rheumatologie & Nephrologie
Zentrale Aufnahme & Erstversorgung (ZAE)
Klinikum Klagenfurt am Wörthersee
“OPTIMIS - Global Observational Study on the use ofSorafenib after TACE in HCC ”
“LINC”, Leipzig 230119
• Advisory board fees from AbbVie, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Ipsen, Lilly, Merck Sharp & Dohme, and Roche
• Grants from AbbVie, ArQule, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, ImClone Systems, Lilly, Merck Sharp & Dohme, Novartis, and Roche
• Consultancy fees from Bayer
• Honoraria from Bayer
Disclosures – Markus Peck-Radosavljevic
• The OPTIMIS study was designed to assess the outcomes of patients with HCC treated with TACE, followed or not followed by sorafenib, in real-world clinical practice
• The study enrolled patients classified as BCLC stage B or higher; all treatment decisions, including TACE and sorafenib, were made by the investigating physician
OPTIMIS study designClinicalTrials.gov NCT01933945
*Includes patients treated with sorafenib at a later time point and patients who were never treated with sorafenib.BCLC, Barcelona Clinic Liver Cancer; BSC, best supportive care; TACE, transarterial chemoembolization.
Sorafenib treatment schema in the OPTIMIS study
CountyTotal
N=1650
n %
Austria 33 2.0
Brazil 12 0.7
Canada 50 3.0
Switzerland 6 0.4
China 150 9.1
Denmark 42 2.5
Egypt 74 4.5
France 209 12.7
Greece 75 4.7
Hungary 11 0.9
Indonesia 32 2.1
India 53 1.9
Japan 233 14.1
Kazakhstan 32 1.9
Korea 292 17.7
Mexico 7 0.4
The Netherlands 3 0.2
Pakistan 57 3.5
Russian Federation 33 2.0
Singapore 26 1.6
Slovakia 4 0.2
Sweden 31 1.9
Thailand 32 1.9
Taiwan 123 7.5
Vietnam 30 1.8
Participating countries and the number of
patients included in the final analysis by country
Source Table 14.1.2 / 1: Demography TCE- Overall TACE population
*Asia excluding China, Japan, and Korea.
• TACE ineligibility was determined using 4 criteria: AASLD (2011)1, JSH (2010)2, protocol-specified (based on multiple international guidelines and expert consensus), and protocol-specified excluding ECOG PS
• JSH TACE-refractory criteria specify failure to TACE but do not include liver function, while AASLD criteria include liver lesions and liver function
TACE ineligibility criteria sets
*As seen ≥4 weeks post TACE by response evaluation using computed tomography; † Depositions (50%) of lipiodol.AASLD, American Association for the Study of Liver Diseases; BCLC, Barcelona Clinic Liver Cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; EHS, extrahepatic spread; JSH, Japan Society of Hepatology; PVT, portal vein thrombosis; TACE, transarterial chemoembolization. 1. Bruix J, et al. Hepatology 2011;53:1020–1022; 2. Kudo M, et al. Dig Dis 2011;29:339–364.
Major differences between the 4 TACE ineligibility criteria sets1. AASLD-based criteria (2011)1
2. JSH-based criteria (2010)2
3. Protocol-specified criteria
4. Protocol-specified excl.
ECOG PS criteria
Contraindications including vascular invasion, PVT, and EHS (N1, M1) X X X X
ECOG PS ≥1 X
BCLC stage C or D X X X
TACE failure by investigator’s assessment X X X
Response to TACE*≥2 consecutive incomplete necrosis† within treated tumors≥2 consecutive new lesions (recurrence) in liver
XX
XX
XX
Patient disposition
The primary analysis population excluded patients with prior sorafenib treatment. TACE ineligibility was determined using collected data by our study protocol-specified criteria according to international guidelines and expert consensus. *All 47 patients allocated to Cohort 1 received sorafenib; †Of the 460 patients allocated to Cohort 2, 97 received sorafenib and 363 did not receive sorafenib at all.TACE, transarterial chemoembolization.
• Overall, 1650 patients received TACE
• 636 patients (39%) were TACEineligible at inclusion according to our study protocol-specified criteria
• Of the 1014 patients TACE eligible at inclusion, 507 patients (50%; 31% of total cohort) became TACE ineligible during the study (primary analysis population)– 47 patients (9%) received sorafenib
at the time of TACE ineligibility (Cohort 1)
– 460 patients (91%) did not receive sorafenib at TACE ineligibility or did not receive sorafenib at all (Cohort 2)
Patients With a Contraindication for TACE According to International Guidelines at Baseline (When Starting First TACE)
39
53
14
82
37
43
24
39
10
37
17
26
13
27
5
68
2624
0 1 0.6 0.7 0 0.6
5 61
41
1511
24
0.6
24
86
0
10
20
30
40
50
60
70
80
90
100
EU and Canada (n=318) Asia (n=208) Japan (n=172) China (n=138) Korea (n=141) Total (N=977)
Pat
ien
ts, %
Overall
ECOG PS ≥1
BCLC C or D
Advanced Liver Disease(Child-Pugh C)
Vascular Invasion
Extrahepatic Spread
Patients could have >1 contraindication.
The proportion of patients with liver function deterioration in the chronic period (31–90 days) was similar to that in the acute period (0–30 days) for the majority of parameters
Liver function deterioration after first TACE
ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio; TACE, transarterial chemoembolization.
Liver function deterioration after first TACE according to TACE eligibility at inclusion
• Liver function deterioration was assessed in patients with at least one liver-related laboratory value for each period: pre-TACE, acute, and chronic. The acute and chronic values were defined as the worst value in their respective time periods, and pre-TACE was defined as the latest value within the 30 days before TACE.ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio; TACE, transarterial chemoembolization.
• Cheng AL et al. Poster PE-066 at: tte 9th Asia-Pacific Primary Cancer Expert Meeting, July 6–8, 2018, Seoul, South Korea.
TACE ineligibleTACE eligible
Liver function deterioration after first TACE according to BCLC stage at inclusion
• Liver function deterioration was assessed in patients with at least one liver-related laboratory value for each period: pre-TACE, acute, and chronic. The acute and chronic values were defined as the worst value in their respective time periods, and pre-TACE was defined as the latest value within the 30 days before TACE.
• ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; INR, international normalized ratio; TACE, transarterial chemoembolization.• Cheng AL et al. Poster PE-066 at: tte 9th Asia-Pacific Primary Cancer Expert Meeting, July 6–8, 2018, Seoul, South Korea.
BCLC stage CBCLC stage B
Radiologic tumor response to each TACE treatment
Complete and partial response rates reduced with each TACE treatment, and progressive disease rate increased by number of TACE procedures
TACE, transarterial chemoembolization.
• After balancing the 2 cohorts according to patient characteristics, a longer median OS was observed for patients in Cohort 1 versus Cohort 2
OS in patients with and without early start of sorafenib
Before matching After matching
nNumber of events, n
(%)
Median OS, months(95% CI)
nNumber of events, n
(%)
Median OS, months(95% CI)
Cohort 1: Patients with early start of sorafenib immediately following TACE ineligibility
47 21 (45)16.2
(10.4, *)31 15 (48)
16.2(10.5, *)
Cohort 2: Patients without early start of sorafenib following TACE ineligibility
460 206 (45)19.8
(15.6, 23.4)62 31 (50)
12.1(10.2, 22.4)
*Presents censored observation or inestimable due to censored data.CI, confidence interval; OS, overall survival; TACE, transarterial chemoembolization.
• A significant number of patients were treated with TACE despite being ineligible at inclusion
• After first TACE, liver function deterioration was noted in both the acute and chronic periods across all assessed liver parameters
• Radiologic tumor response rates reduced with each TACE treatment
• Following TACE ineligibility, systemic therapy was not commonly used and timing to initiation varied
• After propensity score matching, a trend towards a longer OS was observed in patients with versus without early start of sorafenib
• These data highlight a need for a global consensus on appropriate TACE use
Conclusions
BCLC, Barcelona Clinic Liver Cancer; EHS, extrahepatic spread; PVT, portal vein thrombosis; TACE, transarterial chemoembolization.
• We would like to thank the patients who participated in the OPTIMIS study and their families
• We thank the OPTIMIS investigators and members of the OPTIMIS Steering Committee
• OPTIMIS was sponsored by Bayer
14International Liver Cancer Association (ILCA) 12th Annual Conference, Sept 14–16, 2018, London, UK
Acknowledgments
HCC
Baseline characteristics at inclusion visit
Overall TACE population N=1650
Child–Pugh score, n (%)A (5–6 points) + non-cirrhoticB (7–9 points)C (10–15 points)Other/missing
1126 (68) 332 (20)
7 (
• TACE ineligibility at inclusion visit was determined using our study protocol-specified criteria according to international guidelines and expert consensus
• Liver function deterioration was assessed in the acute (0–30 days) and chronic (31–90 days) periods following first TACE and was defined as worsening of CTCAE grade compared with baseline for any of total bilirubin, albumin, AST and ALT*
– Worsening of any of the liver-related parameters constituted liver deterioration
• Radiologic response after each TACE was determined by investigator assessment
• OS from the time of TACE ineligibility was assessed only in the primary analysis population
– To account for the imbalances in patient disease characteristics at the time of TACE ineligibility, a 1:2 propensity score match was utilized
– OS following TACE ineligibility was analyzed for the unmatched and matched populations
International Liver Cancer Association (ILCA) 12th Annual Conference, Sept 14–16, 2018, London, UK
Methods
*Liver function deterioration was assessed in patients with at least one liver-related value for each period: pre-TACE, acute, and chronic. The acute and chronic values were defined as the worst value in their respective time periods and pre-TACE was defined as the latest value within 30 days before TACE.ALT, alanine transaminase; AST aspartate transaminase; CTCAE, Common Terminology Criteria for Adverse Events; OS, overall survival; TACE, transarterial chemoembolization.
Prim. Univ. Prof. Dr. Markus Peck-Radosavljevic
Abteilung Innere Medizin & Gastroenterologie (IMuG)
Hepatologie, Endokrinologie, Rheumatologie & Nephrologie
Zentrale Aufnahme & Erstversorgung (ZAE)
Klinikum Klagenfurt am Wörthersee
“OPTIMIS - Global Observational Study on the use ofSorafenib after TACE in HCC ”
“LINC”, Leipzig 230119
