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.
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DOI：
10.1038/s41416-020-01116-9
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发表时间：
2021-01
影响因子：
8.8
通讯作者：
Sharma R
中科院分区：
文献类型：
--
作者：
Hajiev S;Allara E;Motedayеn Aval L;Arizumi T;Bettinger D;Pirisi M;Rimassa L;Pressiani T;Personeni N;Giordano L;Kudo M;Thimme R;Park JW;Taddei TH;Kaplan DE;Ramaswami R;Pinato DJ;Sharma R
索拉非尼给药对老年肝细胞癌（HCC）患者疗效和毒性的影响尚未达成共识。老年患者通常根据经验开始低剂量治疗，目的是避免毒性，同时最大限度地提高临床疗效。我们的目的是验证年龄是否影响总生存期（OS），以及降低起始剂量是否影响OS或老年人经历的毒性。在一项国际多中心队列研究中，确定了年龄<75岁或≥75岁患者的结局，同时在单变量和多变量模型中考虑了常见的预后因素和人口统计学特征。招募了5598例患者; 792例（14.1%）年龄≥75岁。老年人更可能有较大的肿瘤（>7 cm）（39 vs 33%，p < 0.01），肝功能保留（67 vs 57.7%）（p < 0.01）。年龄≥75岁和<75岁患者的中位OS无差异（7.3个月vs 7.2个月; HR 1.00（95% CI 0.93-1.08），p = 0.97）。索拉非尼800 mg和400 mg/200 mg的起始剂量与<75岁和≥75岁患者的OS之间无相关性。与<75岁的患者相比，老年患者2-4级索拉非尼相关毒性的总体发生率相似（63.5% vs 56.7%，p = 0.11）。然而，老年人更可能因毒性而停用索拉非尼（27.0% vs 21.6%，p < 0.01）。这在索拉非尼的不同起始剂量之间没有变化。老年患者的临床结局与年龄<75岁的患者相当，与索拉非尼处方剂量无关。
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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