Liver Cancer and Clinical Trials

Transcription

1 Liver Cancer and Clinical Trials Abby Siegel MD, MS Medical Director, Hepatobiliary Oncology Columbia University Medical Center Tony Wang MD Assistant Professor, Radiation Oncology, Columbia University Medical Center Why are we Here? We received a grant from the NIH to help educate potentially underserved populations about clinical trials 1. Explain HCC (hepatocellular carcinoma) epidemiology and treatment as the major risk factor from chronic HBV 2. Explain different types of trials and how they help advance care, with HCC as an example 1

2 Asians (Particularly Chinese Americans) are less Likely to Participate in Clinical Trials Barriers include: Not understanding what a clinical trial is Language barrier Mistrust of medical system Inadequate social and financial support Limkakeng, et al, PLOS One, 2013; Tu et al, Cancer 2005 What is a Trial? Research studies that involve people to: Treat a disease Find and diagnose a disease Prevent a disease (vaccination for HBV) Manage symptoms of a disease, or side effects from its treatment 2

3 Types of Clinical Trials Phase I: dose finding, looks for safety Usually people Phase II: tries to look at a small population at one dose, for one disease Usually <100 people Phase III: usually randomized against standard of care Usually > 100 to several thousand Who is Watching Out for Me? The informed consent process Careful review and approval of the clinical trial protocol by: Scientific experts An institutional review board (IRB) Ongoing monitoring of the trial by: The IRB Data and Safety Monitoring Boards (DSMBs) The organization sponsoring the trial The research team 3

4 What to Ask your Doctor? What is the purpose of the trial? What are possible risks and benefits? How do these risks and benefits compare with standard treatment? What kinds of tests and treatments are involved? Who will pay for which parts of the study? Liver Cancer Worldwide El-Serag, NEJM 2011; 365:

5 HCC Risk Factors Exposures Hepatitis B, Aflatoxin HCV, Alcohol use Genetic susceptibility hereditary hemochromatosis, alpha-1 antitrypsin deficiency, Wilson s disease Metabolic factors Obesity, diabetes Demographics Older age, males Epidemiology of HBV Infection HBV is 50 to 100 times more infectious than human immunodeficiency virus type 1 (HIV-1) 1 2 billion people worldwide have been infected with HBV 2 An estimated million people have chronic hepatitis B (CHB) 2,3 Approximately 2-3 million people in the US have CHB 2,3 Increased prevalence of CHB is found in Asian populations 4 ~1 of 8 Vietnamese Americans ~1 of 10 Chinese Americans ~1 of 12 Korean Americans HBV is the second most important carcinogen after tobacco 5 70% of HBV-related deaths are due to hepatocellular carcinoma 6 1. World Health Organization. Fact sheet. Accessed June 26, Gish RG and Gadano AC. J Viral Hepatitis. 2006;13: Welch S, et al. Poster 853 presented at: The Liver Meeting th AASLD Annual Meeting. October 31-November 4, 2008; San Francisco, CA. 4. American Liver Foundation. Hepatitis B and the Asian Community. Accessed January 9, CDC. Epidemiology and Prevention of Vaccine-Preventable Diseases.10 th ed. Accessed January 12, Asian Liver Center Physician s Guide to Hepatitis B. Accessed January 9,

6 Impact of HBV Vaccination 1958 HCC patients, aged 6-29 in Taiwan Information on HCC cases diagnosed between July 1, 1983 and June 30, 2004 obtained from national registry Divided into vaccinated or unvaccinated based on birthdate (July 1, 1984) Vaccinated children much less likely to develop HCC Chang et al, JNCI 2009; 101: Aflatoxin: China s Aflatoxin in milk: now found in cooking oil too Asian Business Daily 5/5/12 6

7 Who Should be Screened? Anybody with cirrhosis What if not Cirrhotic? Asian male HBV carriers over age 40 Asian female HBV carriers over age 50 HBV carrier with family history of HCC 7

8 Liver lesion in a cirrhotic HCC <1 cm >1 cm Growing changing Repeat US 3 months Stable 4 phase CT or dynamic contrast enhanced MRI Arterial hypervascularity and venous or delayed phase washout Investigate according to size Yes AFP is no longer needed for diagnosis! HCC Another scan, (Different Modality) Arterial hypervascularity and venous or delayed phase washout Yes No No Biopsy Cirrhosis and HCC: Two Diseases Photos courtesy of Andrew Zhu, MD, PhD 8

9 HCC DIAGNOSIS & TREATMENT - In cirrhotic patient with characteristic CT or MRI. Llovet J et al. J Nat Cancer Inst Have cirrhosis People who do best with liver transplantation If only one tumor, 5 cm or less 3 or fewer tumors, each 3 cm or less No large blood vessel invasion Mazzafero et al. NEJM 1996, 334:

10 Local Therapies Ablation (burning the tumor): Uncontrolled data suggest ablation equivalent to resection for small HCCs Slide courtesy of Milan Kinkhabwala, MD Local Blood Vessel Treatment (Chemoembolization) The normal liver has two different ways to get blood Tumors receive almost all of their blood supply from one of these ways: the hepatic artery Blocking off the hepatic artery with chemotherapy Now also using Y90 labeled beads ( TheraSphere ) 10

11 Chemoembolization Advanced Disease: Chemotherapy Historically Disappointing Difficult to give chemotherapy with liver compromise Overexpression of MDR-1 gene ( Drug Resistance ) Targets until now have been poorly defined 11

12 Molecularly Targeted Therapy for HCC Siegel et al, Hepatology 52: , 2010 Sorafenib Improves overall survival by about 3 months Doubled time to cancer growth in US 6 vs 3 months FDA approves sorafenib for inoperable HCC

13 Sorafenib in the West: Survival Increased from 7.9 to 10.7 months Llovet et al, NEJM 2008 Side Effects Hand-foot reaction 21% Diarrhea 39% Decreased appetite 14% Bleeding 7% (p=0.07) 13

14 Sorafenib Development Illustrates Types of Trials 1. First dose-finding studies were done Phase I trials 2. Smaller studies done to look more carefully at toxicity Phase II Trials Finally, two large trials were done to see if survival was better in the drug arm Phase III trials Because People were Willing to Participate We now have the first ever approved therapy for liver cancer This is the way we make progress for all kinds of medical treatments 14