Is the efficacy of sorafenib treatment in patients with hepatocellular carcinoma affected by age?

Abstract

Cancer is a prevalent disease in the elderly population and hepatocellular carcinoma (HCC) is a major health problem among all tumors. Curative treatments for early-stage include liver transplantation, resection and percutaneous ablation. Transarterial chemoembolization (TACE) and sorafenib, classified as non-curative treatments, can improve survival for patients with intermediate and advanced tumors, respectively. Even if the incidence of HCC progressively increases with advanced age in all populations, reaching a peak at 70 years, few reports concerning correct management of HCC in elderly patients exist. Moreover, data from large randomized controlled trials (RCT) poorly reflect the elderly population that is often quantitatively and qualitatively underrepresented, as a result of the presence of tight enrolment criteria. The aim of this brief review is to highlight the main concerns, pitfalls and warnings regarding the management of HCC in elderly patients, with particular focus on systemic therapy with sorafenib.

Keywords::

• elderly
• hepatocellular carcinoma
• safety
• sorafenib
• treatment

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Cancer is a prevalent disease in the elderly population: 60% of incident cancer cases and 70% of mortality occurs in patients >65 years of age.

• • Many elderly individuals can be considered clinically ‘fragile’ or ‘vulnerable’, due to their lifetime accumulation of one or more chronic disease with a lower use of aggressive cancer treatments, including surgery, chemotherapy and radiation therapy.

• • Among all cancers, hepatocellular carcinoma (HCC) is a major health problem. It is the sixth most common tumor, and the third most common cause of cancer-related death worldwide.

• • Even if the incidence of HCC increases progressively with advanced age in all populations, reaching a peak at 70 years, few reports concerning correct management of HCC in elderly patients exist.

• • Sorafenib has been established as the first-line systemic treatment in patients with advanced HCC, or intermediate HCC that is not eligible to, or after failure of, locoregional therapies.

• • To date, few data exist in the literature regarding the impact of age on survival and on effectiveness of therapies in elderly patients.

• • Several lines of evidence show that age per se is not an independent risk factor for mortality in HCC. Nevertheless, age itself and associated diseases may influence the therapeutic choices and the allocation to treatment.

• • Three recent studies have demonstrated that treatment with sorafenib is effective regardless of age, with a potential reduced tolerance in older patients, which require more frequent dose adjustments and a closer follow-up.

• • According to recent evidences, treatment with sorafenib should be strongly considered also in patients aged >70 years.

• • Waiting for data on pharmacokinetic/pharmacodynamic analysis in individual patients in clinical practice, adjusted-dose sorafenib may have implications for personalized therapy, especially in ‘fragile’ patients such as elderly ones and those with comorbidities.