Liver and biliary tract cancers -...
Transcript of Liver and biliary tract cancers -...
Liver and biliary
tract cancers
Highlights
Teresa Troiani MD, PHD
U.O.C. OncoEmatologia
Seconda Università degli Studi di Napoli
HIGHLIGHTS
Immunotherapy in Advanced Hepatocellular
carcinoma (HCC)
Adjuvant treatment in Biliary Tract Cancer (BTC)
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
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
Immune therapy is coming of age
William Colet, MD 1892 November 25, 1985 December 20, 2013
Slide courtesy of Jeddy Wolchock/Taha Merghoub
CTLA-4 and PD1/PD-L1 combination therapy
Somatic Mutation Prevalence across Human Cancer
Alexandrov, LB, et al. Nature 2013
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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* Concordance rates between investigator and BIRC was 88.5%
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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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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
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
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
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.
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
PATIENTS AND TUMORS
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
Adverse events
Main toxicities >grade 2
Relapse-Free Survival
Median FU: 44.3 months
HR= 0.83 (95% CI:0,58-1.19), p=0.31
Relapse-Free Survival: predefined subgroups
Quality of Life
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