Liver and biliary

tract cancers

Highlights

Teresa Troiani MD, PHD

U.O.C. OncoEmatologia

Seconda Università degli Studi di Napoli

troiani.teresa@unina2.it

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