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Liver and biliary
tract cancers
Highlights
Teresa Troiani MD, PHD
U.O.C. OncoEmatologia
Seconda Università degli Studi di Napoli
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HIGHLIGHTS
Immunotherapy in Advanced Hepatocellular
carcinoma (HCC)
Adjuvant treatment in Biliary Tract Cancer (BTC)
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Background
Hepatocellular carcinoma (HCC) is among the leading causes of
cancer-related death.1
HCC primarily develops from cirrhosis and most patients are
infected with hepatitis virus type C (HCV) or B (HBV).2
Patients with advanced HCC have a high unmet need, and
treatment with multikinase inhibitor sorafenib is the only systemic
therapy option.
Is there any role for the immunotherapy?
1. International Agency for Research on Cancer. GLOBOCAN2012v1.0.http://globocan.iarc.fr/Pages/fact-
sheets-population.aspx.AccessedMarch 18,2016.
2. McGlynn KA et al. Clin Liver Dis. 2015; 19:223-238.
Immunotherapy in Advanced Hepatocellular Carcinoma
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Occurrence in chronically infected livers-immunosuppressed
Immune cell subsets may be prognostic (TH-2 signature)
Spontaneous immunity: abscopal response, relationship between
autoimmune disease and HCC
Immune response to local tumor ablation
Biologics/antibodies do not require hepatic metabolism
Rational
Immunotherapy in Advanced Hepatocellular Carcinoma
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Immune therapy is coming of age
William Colet, MD 1892 November 25, 1985 December 20, 2013
Slide courtesy of Jeddy Wolchock/Taha Merghoub
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CTLA-4 and PD1/PD-L1 combination therapy
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Somatic Mutation Prevalence across Human Cancer
Alexandrov, LB, et al. Nature 2013
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PD1-PDL-1 Axis in HCC
1)Tasumi et al. Hepatology 1997 Gao Q et al. Clin Cancer Res 2009; 3) Wang et al. World J. Gastroenterol. 2011; 4) Gao et al Clinical Cancer Res 2009,
5) Zeng Plos one 2011; 6) Kuang D et al. J exp Med 2009; 7) Wu K et al. Cancer Res 2009
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Slide 4
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Slide 5
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Slide 6
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Slide 7
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Slide 8
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Slide 9
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Slide 10
* Concordance rates between investigator and BIRC was 88.5%
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Slide 11
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Slide 12
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Slide 13
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Slide 14
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Slide 15
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Slide 16
OS rates at 6 and 9 months in sorafenib-naive patients treated in
the dose-expansion phase were 87% and 77%, respectively.
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Slide 17
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Nivolumab treatment was feasible: Toxicities as
expected and manageable.
Nivolumab demonstrated: Objective responses and long-
term survival in sorafenib treated and naïve patients.
Nivolumab treatment demonstrated: No detrimental
effect in quality of life.
Immunotherapy in advanced HCC has
come of age
Immunotherapy in Advanced Hepatocellular Carcinoma
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Background
11,420 new cases of Biliary Cancer diagnosed
3,710 deaths from these cancers occurred
Most diagnosed at an advanced disease stage
Only 1 in 5 diagnosed with resectable disease
Adjuvant Treatment in Biliary Tract Cancer
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Rational
High risk of relapse following surgery for localized Biliary Tract
Cancer
5-yr OS=31% in resected intrahepatic cholangiocarcinoma;
Median survival =27 months1
No proven (neo)-adjuvant treatment exists
In the palliative setting:
-Combination of gemcitabine-cisplatin improves Overall Survival (ABC-022 and
BT223)
-GEMOX is considered an active regimen based on data from phase II trials4
1De Jong et al .J Clin Oncol 2011; 2Valle NEJM 2010; 3Okusaka Brit J Cancer 2010; 4 Andre Brit J Cancer 2008
Adjuvant Treatment in Biliary Tract Cancer
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GEMOX vs surveillance following surgery
of localized biliary tract cancer: results of
the PRODIGE 12 - ACCORD 18
(UNICANCER GI) phase III trial
Presented By Julien Edeline at 2017 Gastrointestinal Cancers Symposium
DESIGN
Stratification factors: tumor site(ICC vs ECC/Hilar vs GBC); R0 vs R1; N0 vs N+ vs NX; center.
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2 Co-primary endpoints
• Relapse-free survival (RFS)
• Quality of life
Hypothesis: Increase median RFS from 18 to 30 mos
(HR=0.60)
Secondary endpoints: OS, DFS, Tolerability/Toxicity,
Translational research
EndpointsBTC
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PATIENTS AND TUMORS
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Treatment
GEMOX Arm:
- Median of 12 cycles
- Mean of 9.3 cycles
-Median of 10 cycles with oxaliplatin
-Mean of 8.5 cycles with oxaliplatin
-31/94 patients (33.0%) had 12 cycles with GEMOX
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Adverse events
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Main toxicities >grade 2
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Relapse-Free Survival
Median FU: 44.3 months
HR= 0.83 (95% CI:0,58-1.19), p=0.31
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Relapse-Free Survival: predefined subgroups
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Quality of Life
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Adjuvant GEMOX was feasible:
Toxicities as expected and manageable;
No detrimental effect in quality of life.
RFS no different between the two arms
No role for adjuvant in resected biliary tract
especially for low-risk cases
Adjuvant Treatment in Biliary Tract Cancer