Purpose Sorafenib is currently the only Food and Drug Administration-approved first-line therapy for patients with advanced hepatocellular carcinoma. There are few data examining how sorafenib starting dose may influence patient outcomes and costs. Patients and Methods We retrospectively evaluated 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. After 1:1 propensity score matching to account for potential treatment bias, hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. A matched multivariate logistic regression was performed to adjust for potential confounders. The primary end point was overall survival (OS) of patients who were prescribed standard starting dosage sorafenib (800 mg/d per os) versus that of patients who were prescribed reduced starting dose sorafenib (< 800 mg/d per os). Results There were 3,094 standard dose sorafenib patients (63%) and 1,809 reduced starting dose sorafenib patients (37%). Reduced starting dose sorafenib patients had more Barcelona Clinic Liver Cancer stage D ( P < .001), higher Model for End-Stage Liver Disease Sodium scores ( P < .001), higher Child-Turcotte-Pugh scores ( P < .001), and higher Cirrhosis Comorbidity Index scores ( P = .01). Consequently, reduced starting dose sorafenib patients had lower OS (median, 200 v 233 days, HR = 1.10). After propensity score matching and adjusting for potential confounders, there was no longer a significant OS difference (adjusted hazard ratio [HRadj], 0.92; 95% CI, 0.83 to 1.01), and this fell significantly below the noninferiority margin ( P < .001). Reduced starting dose sorafenib patients experienced significantly lower total cumulative sorafenib cost and were less likely to discontinue sorafenib because of gastrointestinal adverse effects (8.7% v 10.8%; P = .047). Conclusion The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior OS relative to standard dosing.

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索拉非尼治疗肝细胞癌的起始剂量：一项回顾性、多机构研究

目的索拉非尼是目前唯一获得食品和药物管理局批准的晚期肝细胞癌患者的一线治疗药物。很少有数据研究索拉非尼的起始剂量如何影响患者的结果和成本。患者和方法 我们回顾性评估了 2006 年 1 月至 2015 年 4 月期间从 128 家退伍军人健康管理局医院接受索拉非尼治疗肝细胞癌的 4,903 名患者。在 1:1 倾向评分匹配以考虑潜在的治疗偏倚后，使用Cox 回归并针对 HR = 1.1 的非劣效性边际进行了测试。进行匹配的多变量逻辑回归以调整潜在的混杂因素。主要终点是服用标准起始剂量索拉非尼（800 mg/d 口服）的患者与服用降低起始剂量索拉非尼（< 800 mg/d 口服）的患者的总生存期（OS）。结果 共有 3,094 名标准剂量索拉非尼患者 (63%) 和 1,809 名降低起始剂量索拉非尼患者 (37%)。降低起始剂量的索拉非尼患者有更多的巴塞罗那临床肝癌 D 期 ( P < .001)、更高的终末期肝病模型钠评分 ( P < .001)、更高的 Child-Turcotte-Pugh 评分 ( P < .001)和更高的肝硬化合并症指数评分 (P = .01)。因此，降低起始剂量的索拉非尼患者的 OS 较低（中位数，200 天对 233 天，HR = 1.10）。在倾向得分匹配和调整潜在的混杂因素之后，不再有显着的 OS 差异（调整后的风险比 [HRadj]，0.92；95% CI，0.83 至 1.01），这显着低于非劣效性界限 (P < .001)。降低起始剂量的索拉非尼患者的总累积索拉非尼成本显着降低，并且不太可能因为胃肠道不良反应而停用索拉非尼（8.7% 对 10.8%；P = .047）。结论 以减少的剂量开始索拉非尼治疗与减少药丸负担、降低治疗成本以及因不良事件而停止索拉非尼的比率呈下降趋势相关。与标准剂量相比，减少剂量与较差的 OS 无关。降低起始剂量的索拉非尼患者的总累积索拉非尼成本显着降低，并且由于胃肠道不良反应而停用索拉非尼的可能性较小（8.7% 对 10.8%；P = .047）。结论 以减少的剂量开始索拉非尼治疗与减少药丸负担、降低治疗成本以及因不良事件而停止索拉非尼的比率呈下降趋势相关。与标准剂量相比，减少剂量与较差的 OS 无关。降低起始剂量的索拉非尼患者的总累积索拉非尼成本显着降低，并且由于胃肠道不良反应而停用索拉非尼的可能性较小（8.7% 对 10.8%；P = .047）。结论 以减少的剂量开始索拉非尼治疗与减少药丸负担、降低治疗成本以及因不良事件而停止索拉非尼的比率呈下降趋势相关。与标准剂量相比，减少剂量与较差的 OS 无关。降低了治疗成本，并且由于不良事件而停止索拉非尼的比率呈下降趋势。与标准剂量相比，减少剂量与较差的 OS 无关。降低了治疗成本，并且由于不良事件而停止索拉非尼的比率呈下降趋势。与标准剂量相比，减少剂量与较差的 OS 无关。