Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: age is not a problem

Ziogas, Dimitrios C.; Papadatos-Pastos, D.; Thillai, Kiruthikah; Korantzis, Ioannis; Chowdhury, R; Suddle, Abid; O’Grady, John; Al-Khadimi, Gillian; Allen, Natalie; Heaton, Nigel; Ross, Paul; Sarker, Debashis

doi:10.1097/meg.0000000000000739

Cited by 18 publications

(18 citation statements)

References 27 publications

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“…However, there is conflicting evidence for this practice and no consensus on the recommended starting dose. 10 , 14 , 16 , 19 , 20 , 24 We have conducted the largest international study investigating the impact of sorafenib dosing in an elderly population, comparing clinical outcomes to patients aged <75 years.…”

Section: Discussionmentioning

confidence: 99%

“…This in line with a number of smaller studies carried out in Europe and Asia; the strength of this study being that we have considered patients from Asia, Europe and the USA ensuring global representation of aetiologies of HCC and differing prescribing practices. 10 , 14 , 15 , 19 , 25 , 26 While combination therapy is likely to be the new gold standard for the management of HCC, given the relative cost of sorafenib, it is unlikely that many health systems will adopt this immediately and instead will continue to utilise sorafenib.…”

Section: Discussionmentioning

confidence: 99%

“… 30 We also report similar frequency and severity of toxicity between the two age groups, which again reaffirms the data previously published and is in line with the incidence of toxicities reported in the SHARP and Asia-Pacific trials. 10 The only differences of note were anorexia and rash, which was more pronounced in the elderly cohort, a key concern in maintaining quality of life in the elderly.…”

Section: Discussionmentioning

confidence: 99%

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Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study

et al. 2020

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Background There is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC). Older patients are often empirically started on low-dose therapy with the aim to avoid toxicities while maximising clinical efficacy. We aimed to verify whether age impacts on overall survival (OS) and whether a reduced starting dose impacts on OS or toxicity experienced by the elderly. Methods In an international, multicentre cohort study, outcomes for those aged <75 or ≥75 years were determined while accounting for common prognostic factors and demographic characteristics in univariable and multivariable models. Results Five thousand five hundred and ninety-eight patients were recruited; 792 (14.1%) were aged ≥75 years. The elderly were more likely to have larger tumours (>7 cm) (39 vs 33%, p < 0.01) with preserved liver function (67 vs 57.7%) (p < 0.01). No difference in the median OS of those aged ≥75 years and <75 was noted (7.3 months vs 7.2 months; HR 1.00 (95% CI 0.93–1.08), p = 0.97). There was no relationship between starting dose of sorafenib 800 mg vs 400 mg/200 mg and OS between those <75 and ≥75 years. The elderly experienced a similar overall incidence of grade 2–4 sorafenib-related toxicity compared to <75 years (63.5 vs 56.7%, p = 0.11). However, the elderly were more likely to discontinue sorafenib due to toxicity (27.0 vs 21.6%, p < 0.01). This did not vary between different starting doses of sorafenib. Conclusions Clinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study

et al. 2020

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“…Although there are limited data regarding this drug in elderly patients with HCC, most studies suggest that survival gain and severe adverse events are similar to those observed in non-elderly patients with HCC (60,61). However, one study suggested that such events might occur more frequently in elderly patients with HCC than in non-elderly patients (62).…”

Section: Palliative Therapymentioning

confidence: 99%

A Review of Hepatocellular Carcinoma in Elderly Patients Focused on Management and Outcomes

Cho

Jun

et al. 2019

In Vivo

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Recent studies report a significant age-specific increase in hepatocellular carcinoma (HCC) development among persons over 75 years old. Therefore, there is an urgent need to determine the optimal treatment strategy in elderly patients with HCC. This systemic review examines the clinical characteristics, efficacy, and safety of first-line treatment modalities. The literature was searched regarding epidemiology and clinical outcomes in elderly patients (age ≥75 years) undergoing first-line treatment for HCC. Causative or comorbid conditions of HCC in elderly patients differed from those in younger patients. Radiofrequency ablation may be effective and safe in early stages. Surgical resection may also be feasible in the early stages for selected patients. Transarterial chemoembolization may be safe and effective for intermediate HCC, and sorafenib may be feasible in elderly patients with advanced HCC. Prospective randomized trials are needed to establish the treatment strategy for elderly patients with HCC.

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“…In the real-world setting, Jo et al [39] reported that there were no significant differences in OS, ORR, and frequency and severity of drug-related adverse events (AEs) between elderly patients (≥80 years) and nonelderly patients (<80 years) in both the entire study cohort ( n = 185) and the propensity-matched cohort ( n = 48). Ziogas et al [40] reported similar results, showing that the safety and efficacy of sorafenib did not differ between elderly patients (≥75 years) ( n = 39) and nonelderly patients (<75 years) ( n = 151). In a propensity-matched study, Nishikawa et al [41] reported that OS in elderly patients (≥80 years) ( n = 132) was similar to that in nonelderly patients (<80 years) ( n = 132) (9.3 and 8.8 months, respectively; p = 0.8247).…”

Section: Molecular Targeted Agents: First-line Drugsmentioning

confidence: 74%

Recent Advances in Systemic Therapy for Hepatocellular Carcinoma in an Aging Society: 2020 Update

Kudo¹

2020

Liver Cancer

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Systemic therapy for hepatocellular carcinoma (HCC) has changed markedly since the introduction of the molecular targeted agent sorafenib in 2007. Sorafenib increased the available treatment options for patients with extrahepatic spread and vascular invasion and improved survival in patients with advanced HCC; however, various shortcomings such as low response rates and relatively high toxicity (e.g., hand-foot skin reaction) prompted concerted efforts aimed at developing new molecular targeted agents to provide more treatment options and second-line agents for patients with disease progression or intolerance to sorafenib. Despite many attempts to develop new drugs between 2007 and 2016, all first-line and second-line clinical trials conducted during this period failed. However, between 2017 and 2019, 4 drugs (lenvatinib as a first-line agent and regorafenib, cabozantinib, and ramucirumab as second-line agents) emerged in quick succession from clinical trials and became available for clinical use. In addition, nivolumab and pembrolizumab were approved as second-line agents after sorafenib. A recent phase III trial (IMbrave150) showed that combination immunotherapy with atezolizumab plus bevacizumab increases overall survival compared with sorafenib therapy; Food and Drug Agency already approved this combination therapy, and worldwide approval is expected soon. This review describes the recent advances in systemic therapy and the use of tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib, and cabozantinib), monoclonal antibodies (ramucirumab and bevacizumab), and immune checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) in elderly patients and the similarity of their efficacy and safety profiles to those in the general population.

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Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: age is not a problem

Abstract: Elderly patients with advanced HCC, when treated with sorafenib, have an equivalent clinical outcome with similar toxicity rates as their younger counterparts. Age alone should not be a discriminating factor for the management of advanced HCC with sorafenib.

Cited by 18 publications

References 27 publications

Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study

Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study

A Review of Hepatocellular Carcinoma in Elderly Patients Focused on Management and Outcomes

Recent Advances in Systemic Therapy for Hepatocellular Carcinoma in an Aging Society: 2020 Update

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