Liver and biliary tract cancers - Aiom · Liver and biliary tract cancers ... Slide 16 OS rates at...

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Liver and biliary tract cancers Highlights Teresa Troiani MD, PHD U.O.C. OncoEmatologia Seconda Università degli Studi di Napoli [email protected]

Transcript of Liver and biliary tract cancers - Aiom · Liver and biliary tract cancers ... Slide 16 OS rates at...

Page 1: Liver and biliary tract cancers - Aiom · Liver and biliary tract cancers ... Slide 16 OS rates at 6 and 9 ... Only 1 in 5 diagnosed with resectable disease Adjuvant Treatment in

Liver and biliary

tract cancers

Highlights

Teresa Troiani MD, PHD

U.O.C. OncoEmatologia

Seconda Università degli Studi di Napoli

[email protected]

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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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* 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

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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