A Real-World Observational Cohort of Patients with Hepatocellular Carcinoma: Design and Rationale for TARGET-HCC

Roniel Cabrera, Amit G Singal, Massimo Colombo, R Kate Kelley, Hannah Lee, Andrea R Mospan, Tim Meyer, Pippa Newell, Neehar D Parikh, Bruno Sangro, K Rajender Reddy, Stephanie Watkins, Richard C Zink, Adrian M Di Bisceglie, Roniel Cabrera, Amit G Singal, Massimo Colombo, R Kate Kelley, Hannah Lee, Andrea R Mospan, Tim Meyer, Pippa Newell, Neehar D Parikh, Bruno Sangro, K Rajender Reddy, Stephanie Watkins, Richard C Zink, Adrian M Di Bisceglie

Abstract

This study describes the design of the TARGET-hepatocellular carcinoma (HCC) cohort and descriptive characteristics of the patient population at diagnosis among those who were enrolled in the cohort across academic and community clinical centers. TARGET-HCC is a 5-year, longitudinal, observational cohort of patients with HCC receiving care in usual clinical practice. Redacted clinical information, obtained from medical records, captures the natural history and management of the disease, including the safety and efficacy of treatment interventions used in usual clinical practice. Patients can complete patient-reported outcome measures and provide biological specimens for future translational studies. The TARGET-HCC study includes adults with histologic, cytologic, or radiologic diagnosis of HCC from academic and community centers in both the United States and Europe. A total of 1,841 participants were enrolled between January 9, 2017, and July 23, 2019, at 67 sites in the United States and Europe. To date, the most common liver disease etiology in the cohort continues to be hepatitis C, although nearly half had a nonviral etiology, including alcohol-related liver disease or nonalcoholic steatohepatitis. Most included patients were diagnosed at an early stage (Barcelona Clinic Liver Cancer Stage [BCLC] 0/A), but only approximately one third underwent curative treatment. Systemic therapy has been used in 7.3% of enrolled patients, including 45.7% of those with BCLC stage C tumors. Conclusion: Overall, the TARGET-HCC cohort allows for the assessment of patient characteristics and investigation of new treatment paradigms and sequencing with existing agents as well as novel regimens for HCC.

Trial registration: ClinicalTrials.gov NCT02954094.

© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.

Figures

FIG. 1
FIG. 1
TARGET‐HCC sites in the United States and Europe. Maps illustrating the location of sites in the United States and Europe participating in TARGET‐HCC; 84% of sites are located in the academic setting, 16% of sites are located in the community setting.

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394‐424. Erratum in: CA Cancer J Clin 2020; PMID:32767693.
    1. Villanueva A. Hepatocellular carcinoma. N Engl J Med 2019;380:1450‐1462.
    1. Jemal A, Ward EM, Johnson CJ, Cronin KA, Ma J, Ryerson B, et al. Annual Report to the Nation on the Status of Cancer, 1975‐2014, featuring survival. J Natl Cancer Inst 2017;109:djx030.
    1. Lok AS, Seeff LB, Morgan TR, di Bisceglie AM, Sterling RK, Curto TM, et al.; HALT‐C Trial Group . Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C‐related advanced liver disease. Gastroenterology 2009;136:138‐148.
    1. Younossi Z, Stepanova M, Ong JP, Jacobson IM, Bugianesi E, Duseja A, et al.; Global Nonalcoholic Steatohepatitis Council . Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol 2019;17:748‐755.e3.
    1. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 2019;16:589‐604.
    1. Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 2018;68:723‐750.
    1. European Association for the Study of the Liver . EASL clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182‐236. Erratum in: J Hepatol 2019; PMID:30739718.
    1. Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta‐analysis. PLoS Med 2014;11:e1001624.
    1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J‐F, et al.; SHARP Investigators Study Group . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378‐390.
    1. Kudo M, Finn RS, Qin S, Han K‐H, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first‐line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non‐inferiority trial. Lancet 2018;391:1163‐1173.
    1. Bruix J, Qin S, Merle P, Granito A, Huang Y‐H, Bodoky G, et al.; RESORCE Investigators . Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet 2017;389:56‐66.
    1. Abou‐Alfa GK, Meyer T, Cheng A‐L, El‐Khoueiry AB, Rimassa L, Ryoo B‐Y, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 2018;379:54‐63.
    1. Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, et al.; REACH‐2 study investigators . Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha‐fetoprotein concentrations (REACH‐2): a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet Oncol 2019;20:282‐296.
    1. El‐Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open‐label, non‐comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017;389:2492‐2502.
    1. Zhu A, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, et al.; KEYNOTE‐224 investigators . Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE‐224): a non‐randomised, open‐label phase 2 trial. Lancet Oncol 2018;19:940‐952.
    1. Finn RS, Ryoo B‐Y, Merle P, Kudo M, Bouattour M, Lim HY, et al.; KEYNOTE‐240 investigators . Pembrolizumab As Second‐Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE‐240: A Randomized, Double‐Blind, Phase III Trial. J Clin Oncol 2020;38:193‐202.
    1. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T‐Y, et al.; IMbrave150 Investigators . Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020;382:1894‐1905.
    1. Singal AG, Higgins PD, Waljee AK. A primer on effectiveness and efficacy trials. Clin Transl Gastroenterol 2014;5:e45.
    1. Barritt AS 4th, Gitlin N, Klein S, Lok AS, Loomba R, Malahias L, et al. Design and rationale for a real‐world observational cohort of patients with nonalcoholic fatty liver disease: the TARGET‐NASH study. Contemp Clin Trials 2017;61:33‐38.
    1. Irwin DE, Stucky B, Langer MM, Thissen D, DeWitt EM, Lai J‐S, et al. An item response analysis of the pediatric PROMIS anxiety and depressive symptoms scales. Qual Life Res 2010;19:595‐607.
    1. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999;19:329‐338.
    1. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693‐699.
    1. Kaplan DE, Dai F, Aytaman A, Baytarian M, Fox R, Hunt K, et al.; VOCAL Study Group . Development and performance of an algorithm to estimate the Child‐Turcotte‐Pugh Score from a national electronic healthcare database. Clin Gastroenterol Hepatol 2015;13:2333‐2341.e1‐6.
    1. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649‐655.
    1. Ahmed S, Berzon RA, Revicki DA, Lenderking WR, Moinpour CM, Basch E, et al.; International Society for Quality of Life Research . The use of patient‐reported outcomes (PRO) within comparative effectiveness research: implications for clinical practice and health care policy. Med Care 2012;50:1060‐1070.
    1. Pugh RN, Murray‐Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:646‐649.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera