Real-life multi-center retrospective analysis on nivolumab in difficult-to-treat patients with advanced hepatocellular carcinoma

Abstract

BACKGROUND Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The landscape of the systemic treatment for advanced HCC is changing quickly, and recently, the standard of care became either atezolizumab plus bevacizumab or tremelimumab plus durvalumab in the single tremelimumab regular interval durvalumab regimen. Nivolumab monotherapy has proven to be effective sometimes for advanced HCC and could be a valuable treatment option for patients outside current treatment indications and reimbursement criteria for the standard of care. This is a particular population of interest. AIM To evaluate the real-world effectiveness of nivolumab monotherapy in patients with advanced HCC who are not eligible for other treatment. METHODS We conducted a retrospective, multicentric study including 29 patients with advanced HCC from 3 Belgian tertiary hospitals. All patients had had prior chemotherapy or were intolerant or ineligible for treatments. All study subjects received nivolumab 3 mg/kg in monotherapy, administered once every two weeks intravenously. Treatment continued until disease progression, severe adverse events or death. Data were retrieved from patients’ medical records. The outcome parameters such as radiological response according to response evaluation criteria in solid tumors (RECIST) criteria, the biological response through the evolution of the alpha-fetoprotein (AFP) level, and clinical response considering both the Child–Pugh (CP) score and the World Health Organization (WHO) performance status (PS) were reported. A safety profile was also reported. Statistical analysis was performed using the SPSS Statistics 27 statistical software package. RESULTS The radiological overall response rate (defined as complete or partial response according to the immune RECIST and modified RECIST criteria) to nivolumab monotherapy was 24.1%. The biological overall response rate (defined as a decrease of ≥ 25% in AFP blood level) was 20.7%. Radiological and biological responses were significantly associated both with each other ( P < 0.001) and with overall survival ( P < 0.005 for radiological response and P < 0.001 for biological response). Overall survival was 14.5 mo (+/- 2.1), and progression-free survival was 10.9 mo (+/- 2.3). After 4 mo of treatment, 78.3% of patients remained clinically stable or even showed improvement in WHO PS. Grade 3 adverse events occurred in 17.2% of patients, none had grade 4 adverse events, and no patients ceased nivolumab due to adverse events. CONCLUSION Nivolumab monotherapy is a good treatment choice in frail patients with HCC who are ineligible for the standard of care or other validated systemic treatments.

Immunotherapy Efficacy in Advanced Hepatocellular Carcinoma in a Diverse and Underserved Population in the United States

“…However, available race and ethnicity data revealed limited prevalence of Blacks and Hispanics. 26–28 …”

“…[22][23][24][25] Of note, in all of these trials, Black and Hispanic patients were significantly under-represented, with a prevalence ranging from <1% to 8% in the immunotherapy-treated arms. [21][22][23][24][25][26][27][28][29] Several realworld retrospective and database studies have included patients with poorer functional status (ECOG 2) and/or decompensated liver disease (Child-Pugh Class B or C). However, available race and ethnicity data revealed limited prevalence of Blacks and Hispanics.…”

“…However, available race and ethnicity data revealed limited prevalence of Blacks and Hispanics. [26][27][28] Characteristics of patients in a minority-rich populations in medically underserved areas of the Bronx are markedly different compared to national or international patient cohorts included in seminal clinical trials. 30 The primary objective of this study was to determine the real-world efficacy and tolerability of immune checkpoint inhibitors in HCC patients seen in an underserved predominately Hispanic and African American population in an academic center serving the Bronx.…”