医脉通编译，转载请务必注明出处
2016年6月3-7日，一年一度的美国临床肿瘤学会（American Society of Clinical Oncology，ASCO）年会将在芝加哥举办。6月6日上午的消化系统（非结直肠）肿瘤口头报告专场上，一项摘要号为4003的随机III期研究（CALGB 80802[Alliance]），在晚期肝细胞癌（HCC）患者中将索拉非尼+阿霉素与索拉非尼单药进行比较，医脉通整理如下：
在HCC中一项随机II期研究的探索性分析中，将单纯阿霉素（D）与阿霉素+索拉非尼（D+S）进行比较，结果显示D+S方案可以显著改善总生存期（JAMA，2011）。这项研究在索拉非尼试验中对组织学预后的比较似乎存在希望。CALGB 80802旨在确定与单纯索拉非尼相比较，阿霉素+索拉非尼是否会提供生存期。
经病理证实的晚期HCC患者，他们之前未接受系统性治疗，且Child-Pugh为A级，被随机分配接受D 60mg/m2，每21天+S 400mg PO 每日两次（D+S）或者单独S。对于胆红素≥1.3倍正常值，D和S剂量需要减半。D最大剂量360/m2。该项研究根据病变范围进行分层（局部晚期；转移性），主要终点是总生存期（OS）；次要终点是无进展生存期（PFS）。当480例总体患者有观察到364例事件时，最后的分析发生，90%的P检出中位OS有37%增加（10.7个月增加至14.7个月；单侧α=0.05）。
在累加至346例患者（各173例接受D+S和S）后Alliance DSMB停止了这项研究。每组出现107例事件，中位OS分别为：D+S组，9.3个月（95% CI 7.1-12.9）；S组，10.5个月（95% CI 7.4-14.3），风险比（HR）为1.06（95% CI 0.8-1.4）。D+S组 vs S组的中位PFS是3.6（95% CI 2.8-4.6） vs 3.2个月（95% CI 2.3-4.1），HR值为0.90（95% CI 0.72-1.2）。接受治疗的患者有38例死亡：18例接受D+S死亡，20例接受S死亡。接受D+S治疗有8例[败血症（1），吞咽困难（1），肺炎（1），心脏病（2），肝功能衰竭（2），和未有特殊说明（1）]，接受S治疗有3例[乏力（1），肝功能衰竭（1），继发性恶性肿瘤（1）]，均是与治疗相关的不良事件。最多的3或4级血液学不良事件（AE）发生在37.8%接受D+S的患者和8.1%接受S的患者中。非血液学AEs具有可比性，分别在63.6%和61.5%的患者中。
综上所述，将阿霉素添加到索拉非尼中会带来较高的毒性，不会显著改善总生存期或无进展生存期。索拉非尼中位总生存期约10个月，与之前的报道一致。NCI Grant U10CA180821临床试验信息：NCT01015833。
会议专题》》》2016年ASCO年会专题报道
原文摘要：
Phase III randomized study of sorafenib plus doxorubicin versus sorafenib in patients with advanced hepatocellular carcinoma (HCC): CALGB 80802 (Alliance).（Abstract 4003）
Authors：Ghassan K. Abou-Alfa, Donna Niedzwieski,et al.
Session Type：Oral Abstract Session
Background: An exploratory analysis of a randomized phase II study in HCC comparing doxorubicin (D) alone to doxorubicin plus sorafenib (D+S) showed a significant improvement in overall survival favoring D+S (JAMA, 2011). The results appeared promising compared to the historic outcomes seen in the pivotal sorafenib (S) trials. CALGB 80802 was designed to determine if D+S improved survival compared to S alone.
Methods: Patients with histologically proven advanced HCC, no prior systemic therapy and Child-Pugh A were randomized to receive D 60 mg/m2 every 21 days plus S 400 mg PO twice daily (D+S) or S alone. For bilirubin ≥ 1.3x normal, D and S doses were halved. D was maxed out at 360 mg/m2. The study was stratified by extent of disease (locally advanced; metastatic), the primary endpoint was overall survival (OS); and secondary endpoint progression-free survival (PFS). The final analysis was to occur when 364 events were observed among 480 total patients, with 90% power to detect a 37% increase in median OS (10.7 to 14.7 months; 1-sided α = 0.05).
Results: The Alliance DSMB halted the study after accrual of 346 patients (173 on each of D+S and S) when a futility boundary was crossed at a planned interim analysis. With 107 events in each arm, median OS was 9.3 months (95%CI 7.1-12.9) for D+S, and 10.5 months (95% CI 7.4-14.3) for S with a hazard ratio (HR) 1.06 (95% CI 0.8- 1.4) for D+S vs. S. Median PFS was 3.6 (95% CI 2.8-4.6) and 3.2 months (95% CI 2.3-4.1), respectively (HR = 0.90, 95% CI 0.72-1.2). There were 38 deaths on treatment: 18 on D+S and 20 on S. Among these 8 [sepsis (1), dysphagia (1), pneumonia (1), cardiac (2), hepatic failure (2), and not otherwise specified (1)] on D+S, and 3 [fatigue (1), hepatic failure (1), and a secondary malignancy (1)] on S, were at least possibly related to treatment. A maximum grade 3 or 4 only hematologic adverse events (AE) occurred in 37.8% of patients on D+S and 8.1% of patients on S. Non-hematologic AEs were comparable, in 63.6% and 61.5% of patients, respectively.
Conclusions: The addition of D to S resulted in higher toxicity and did not improve OS or PFS. The S median OS of about 10 months is consistent with previous reports. NCI Grant U10CA180821 Clinical trial information: NCT01015833
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