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Abstract
BackgroundThere 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.MethodsIn 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.ResultsFive 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.ConclusionsClinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.
Highlights
There is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC)
The safety of sorafenib treatment in elderly patients is of particular concern due to comorbidities, impaired organ function, polypharmacy as well as altered pharmacokinetics; sorafenib is metabolised by CYP3A, the activity of which slows with increasing age.[9]
We investigated the impact of the starting dose of sorafenib in the elderly population aged ≥75 years on overall survival (OS) and drug tolerability
Summary
There is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC). 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. Age is a risk factor for developing HCC with the highest agespecific incidence in most Western populations occurring over 75 years, a pattern that is replicated in Asia.[6,7,8] The number of elderly patients with HCC is likely to increase as a result of demographic trends and due to improvements in treatment of chronic liver disease. The safety of sorafenib treatment in elderly patients is of particular concern due to comorbidities, impaired organ function, polypharmacy as well as altered pharmacokinetics; sorafenib is metabolised by CYP3A, the activity of which slows with increasing age.[9] There is a paucity of evidence in terms of safety, efficacy and recommended dosing for the elderly due to their under-representation in clinical trials. It has been suggested that the clinical outcome from sorafenib is not influenced by increasing age.[9,10,11,12,13] In a multicentre study in Japan, 179 patients
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