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.
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.
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.
Clinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.
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Ethics approval and consent to participate
The study protocol was approved by the Yorkshire & The Humber - Sheffield Research Ethics Committee in the UK (Reference 17/YH/0015), as well as the institutional review boards in each participating institution (Supplementary Information 1). The study was conducted in accordance with the Declaration of Helsinki (update 2004). Subjects provided informed consent in centres with prospective data collection, and in centres with retrospective data collection consent was waived by the respective institutional review boards.
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L.R.: consulting and advisory role: Amgen, ArQule, Basilea, Baxter, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Italfarmaco, Lilly, MSD, Roche, Sanofi, Sirtex Medical; honoraria and lectures: AbbVie, AstraZeneca, Gilead; travel expenses: ArQule, Ipsen. D.B.: consulting and advisory: Bayer Healthcare, Boston Scientific; honoria and lectures: Falk Foundation. N.P.: consulting and advisory role: Amgen, Merck Serono, Servier; lectures: AbbVie, Gilead, Lilly; travel expenses: Amgen, ArQule. D.J.P.: research funding: MSD, Bristol-Myers Squibb, Franco Trevisani; consulting and advisory role: Bayer AG, Alfasigma, Bristol-Myers Squibb; lectures: Bayer AG, Roche, Falk Foundation; travel, accommodations, expenses: Bayer AG. R.S.: research funding: Incyte, AAA; consulting and advisory role: Esai, Roche, Bayer AG, SIRTEX; lectures: Bayer AG, Falk Foundation. No other author has any conflict of interest to declare.
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Hajiev, S., Allara, E., Motedayеn-Aval, L. et al. Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-01116-9