Racial and ethnic disparities in early treatment with immunotherapy for advanced HCC in the United States.
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
29
03
2022
received:
22
11
2021
accepted:
04
04
2022
pubmed:
17
4
2022
medline:
16
11
2022
entrez:
16
4
2022
Statut:
ppublish
Résumé
Immunotherapy has emerged as an effective treatment for patients with advanced-stage HCC. We aimed to investigate the efficacy of immunotherapy for advanced HCC in a nationwide cohort and racial and ethnic disparities in access to immunotherapy. We used the US National Cancer Database to identify patients with tumor-node-metastasis stage 3 or 4 HCC between 2017 and 2018. We performed multivariable Cox regression to identify factors associated with overall survival (OS) and logistic regression to identify factors associated with receipt of immunotherapy. Of the 3,990 patients treated for advanced HCC, 3,248 (81.4%) patients received chemotherapy and 742 (18.6%) patients received immunotherapy as a first-line treatment. Immunotherapy was associated with improved OS compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65-0.88) after adjusting for covariates. There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46-0.83) and Black patients (aOR: 0.71, 95% CI: 0.54-0.89) less likely to receive immunotherapy compared with White patients. There was a significant interaction between race-ethnicity and facility type, with higher disparity observed in nonacademic centers (interaction p = 0.004). Immunotherapy was associated with improved OS compared with chemotherapy in advanced HCC. There are significant disparities in early access to immunotherapy, likely due to differential access to clinical trials and experimental therapies. A comprehensive approach to monitoring and eliminating racial-ethnic disparities in the management of advanced HCC is urgently needed.
Sections du résumé
BACKGROUND AND AIMS
Immunotherapy has emerged as an effective treatment for patients with advanced-stage HCC. We aimed to investigate the efficacy of immunotherapy for advanced HCC in a nationwide cohort and racial and ethnic disparities in access to immunotherapy.
APPROACH AND RESULTS
We used the US National Cancer Database to identify patients with tumor-node-metastasis stage 3 or 4 HCC between 2017 and 2018. We performed multivariable Cox regression to identify factors associated with overall survival (OS) and logistic regression to identify factors associated with receipt of immunotherapy. Of the 3,990 patients treated for advanced HCC, 3,248 (81.4%) patients received chemotherapy and 742 (18.6%) patients received immunotherapy as a first-line treatment. Immunotherapy was associated with improved OS compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65-0.88) after adjusting for covariates. There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46-0.83) and Black patients (aOR: 0.71, 95% CI: 0.54-0.89) less likely to receive immunotherapy compared with White patients. There was a significant interaction between race-ethnicity and facility type, with higher disparity observed in nonacademic centers (interaction p = 0.004).
CONCLUSIONS
Immunotherapy was associated with improved OS compared with chemotherapy in advanced HCC. There are significant disparities in early access to immunotherapy, likely due to differential access to clinical trials and experimental therapies. A comprehensive approach to monitoring and eliminating racial-ethnic disparities in the management of advanced HCC is urgently needed.
Identifiants
pubmed: 35429171
doi: 10.1002/hep.32527
pii: 01515467-202212000-00010
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1649-1659Informations de copyright
© 2022 American Association for the Study of Liver Diseases.
Références
Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability‐adjusted life‐years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3:524–548.
Cillo U, Vitale A, Grigoletto F, Farinati F, Brolese A, Zanus G, et al. Prospective validation of the Barcelona Clinic Liver Cancer staging system. J Hepatol. 2006;44:723–731.
Yang JD, Heimbach JK. New advances in the diagnosis and management of hepatocellular carcinoma. BMJ. 2020;371:m3544.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J‐F, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–390.
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;391:1163–73.
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.
Bruix J, Qin S, Merle P, Granito A, Huang Y‐H, Bodoky G, et al. 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.
Zhu AX, Kang Y‐K, Yen C‐J, Finn RS, Galle PR, Llovet JM, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α‐fetoprotein concentrations (REACH‐2): a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet Oncol. 2019;20:282–96.
Sangro B, Sarobe P, Hervás‐Stubbs S, Melero I. Advances in immunotherapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021;18:525–43.
Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE‐224): a non‐randomised, open‐label phase 2 trial. Lancet Oncol. 2018;19:940–52.
Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T‐Y, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–905.
Rimassa L, Cheng A, Braiteh F, Benzaghou F, Hazra S, Borgman A, Sinha R, et al. P‐238 ‐ Phase 3 (COSMIC‐312) study of cabozantinib in combination with atezolizumab vs sorafenib in patients with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy. Ann Oncol. 2019;30:iv65–iv66.
Llovet JM, Kudo M, Cheng A‐L, Finn RS, Galle PR, Kaneko S, et al. Lenvatinib (len) plus pembrolizumab (pembro) for the first‐line treatment of patients (pts) with advanced hepatocellular carcinoma (HCC): phase 3 LEAP‐002 study. J Clin Oncol. 2019;37:TPS4152.
Abou‐Alfa GK, Chan SL, Furuse J, Galle PR, Kelley RK, Qin S, et al. A randomized, multicenter phase 3 study of durvalumab (D) and tremelimumab (T) as first‐line treatment in patients with unresectable hepatocellular carcinoma (HCC): HIMALAYA study. J Clin Oncol. 2018;36:TPS4144.
Hamel LM, Penner LA, Albrecht TL, Heath E, Gwede CK, Eggly S. Barriers to clinical trial enrollment in racial and ethnic minority patients with cancer. Cancer Control J Moffitt Cancer Center. 2016;23:327–37.
Benson AB, D’Angelica MI, Abbott DE, Anaya DA, Anders R, Are C, et al. Hepatobiliary cancers, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19:541–65.
Moore D. Applied survival analysis using R. New York, NY: Springer; 2016. https://doi.org/10.1007/978‐3‐319‐31245‐3
Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika. 1994;81:515–26.
White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med. 2011;30:377–99.
Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350‐1355.
Sangro B, Gomez‐Martin C, de la Mata M, Iñarrairaegui M, Garralda E, Barrera P, et al. A clinical trial of CTLA‐4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. J Hepatol. 2013;59:81–8.
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;389:2492–502.
Yau T, Park JW, Finn RS, Cheng A‐L, Mathurin P, Edeline J, et al. LBA38_PR ‐ CheckMate 459: a randomized, multi‐center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first‐line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Ann Oncol. 2019;30:v874–v875.
Finn RS, Ryoo B‐Y, Merle P, Kudo M, Bouattour M, Lim HY, et al. Pembrolizumab as second‐line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE‐240: a randomized, double‐blind, phase III trial. J Clin Oncol. 2019;38:193–202.
Yau T, Kang Y‐K, Kim T‐Y, El‐Khoueiry AB, Santoro A, Sangro B, et al. Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): results from CheckMate 040. J Clin Oncol. 2019;37:4012.
Kelley RK, Sangro B, Harris WP, Ikeda M, Okusaka T, Kang Y‐K, et al. Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC). J Clin Oncol. 2020;38:4508.
Zhu AX, Finn RS, Ikeda M, Sung MW, Baron AD, Kudo M, et al. A phase Ib study of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC). J Clin Oncol. 2020;38:4519.
Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T‐Y, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–905.
Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang Y‐K, et al. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I/II study. J Clin Oncol. 2021;39:2991–3001.
Osarogiagbon RU, Sineshaw HM, Unger JM, Acuña‐Villaorduña A, Goel S. Immune‐based cancer treatment: addressing disparities in access and outcomes. Am Soc Clin Oncol Educ Book. 2021;66–78.
Duma N, Vera Aguilera J, Paludo J, Haddox CL, Gonzalez Velez M, Wang Y, et al. Representation of minorities and women in oncology clinical trials: review of the past 14 years. J Oncol Pract. 2018;14:e1–e10.
Javier‐DesLoges J, Nelson TJ, Murphy JD, McKay RR, Pan E, Parsons JK, et al. Disparities and trends in the participation of minorities, women, and the elderly in breast, colorectal, lung, and prostate cancer clinical trials. Cancer. 2022;128:770–7.
Diehl KM, Green EM, Weinberg A, Frederick WA, Holmes DR, Green B, et al. Features associated with successful recruitment of diverse patients onto cancer clinical trials: report from the American College of Surgeons Oncology Group. Ann Surg Oncol. 2011;18:3544–50.
Moskowitz GB, Stone J, Childs A. Implicit stereotyping and medical decisions: unconscious stereotype activation in practitioners' thoughts about African Americans. Am J Public Health. 2012;102:996–1001.
Sabin JA, Rivara FP, Greenwald AG. Physician implicit attitudes and stereotypes about race and quality of medical care. Med Care. 2008;46:678–85.
Rivers D, August EM, Sehovic I, Lee Green B, Quinn GP. A systematic review of the factors influencing African Americans’ participation in cancer clinical trials. Contemp Clin Trials. 2013;35:13–32.
Ford JG, Howerton MW, Lai GY, Gary TL, Bolen S, Gibbons MC, et al. Barriers to recruiting underrepresented populations to cancer clinical trials: a systematic review. Cancer. 2008;112:228–42.
Schoenberger H, Rich NE, Jones P, Yekkaluri S, Yopp A, Singal AG, Arroyo A, et al. Racial and ethnic disparities in barriers to care in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2021 Dec 26. https://doi.org/10.1016/j.cgh.2021.12.027 . [Epub ahead of print].
doi: 10.1016/j.cgh.2021.12.027
Eggly S, Barton E, Winckles A, Penner LA, Albrecht TL. A disparity of words: racial differences in oncologist‐patient communication about clinical trials. Health Expect. 2015;18:1316–26.
Guo A, Pomenti S, Wattacheril J. Health disparities in screening, diagnosis, and treatment of hepatocellular carcinoma. Clin Liv Dis. 2021;17:353–8.
Rich NE, Carr C, Yopp AC, Marrero JA, Singal AG. Racial and ethnic disparities in survival among patients with hepatocellular carcinoma in the United States: a systematic review and meta‐analysis. Clin Gastroenterol Hepatol. 2022;20:e267–e288.
Rich NE, Hester C, Odewole M, Murphy CC, Parikh ND, Marrero JA, et al. Racial and ethnic differences in presentation and outcomes of hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2019;17:551–9.
Peters NA, Javed AA, He J, Wolfgang CL, Weiss MJ. Association of socioeconomics, surgical therapy, and survival of early stage hepatocellular carcinoma. J Surg Res. 2017;210:253–60.
Barzi A, Zhou K, Wang S, Dodge JL, El‐Khoueiry A, Setiawan VW. Etiology and outcomes of hepatocellular carcinoma in an ethnically diverse population: the multiethnic cohort. Cancers. 2021;13:3476.
Barzi A, Zhou K, Wang S, Dodge JL, El‐Khoueiry A, Setiawan VW. Etiology and outcomes of hepatocellular carcinoma in an ethnically diverse population: the multiethnic cohort. Cancers. 2021;13:3476.