Andrew X. Zhu, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; Olivier Rosmorduc, Service d'Hépatologie, Hôpital Saint-Antoine, Paris; Marie-Aude Leberre, Bayer HealthCare Pharmaceuticals, Loos, France; T.R. Jeffry Evans, Beatson West of Scotland Cancer Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow; Paul J. Ross, King's College Hospital, London, United Kingdom; Armando Santoro, Humanitas Cancer Center, Milan, Italy; Flair Jose Carrilho, University of São Paulo School of Medicine, São Paulo, Brazil; Jordi Bruix and Josep M. Llovet, Barcelona Clínic Liver Cancer Group, Institut d'Investigacions Biomèdiques, August Pi i Sunyer, Hospital Clínic Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona; Josep M. Llovet, Institució Catalana de Recerca I Estudis Avançats, Catalonia, Spain; Shukui Qin, People's Liberation Army Cancer Center of Nanjing Bayi Hospital, Jiangsu, China; Paul J. Thuluvath, Institute for Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, MD; Josep M. Llovet, Mount Sinai Liver Cancer Program, Mount Sinai School of Medicine, New York, NY; Markus Jensen, Bayer Vital GmbH, Leverkusen, Germany; Gerold Meinhardt, Bayer HealthCare Pharmaceuticals, Montville, NJ; and Yoon-Koo Kang, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
J Clin Oncol. 2015 Feb 20;33(6):559-66. doi: 10.1200/JCO.2013.53.7746. Epub 2014 Dec 29.
To compare the clinical outcomes of sorafenib plus either erlotinib or placebo in patients with advanced hepatocellular carcinoma (HCC) in a multicenter, multinational, randomized, phase III trial.
Patients with advanced HCC and underlying Child-Pugh class A cirrhosis, who were naive to systemic treatment (N = 720), were randomly assigned to sorafenib plus either erlotinib (n = 362) or placebo (n = 358). The primary end point was overall survival (OS).
Median OS was similar in the sorafenib plus erlotinib and sorafenib plus placebo groups (9.5 v 8.5 months, respectively; hazard ratio [HR], 0.929; P = .408), as was median time to progression (3.2 v 4.0 months, respectively; HR, 1.135; P = .18). In the sorafenib/erlotinib arm versus the sorafenib/placebo arm, the overall response rate trended higher (6.6% v 3.9%, respectively; P = .102), whereas the disease control rate was significantly lower (43.9% v 52.5%, respectively; P = .021). The median durations of treatment with sorafenib were 86 days in the sorafenib/erlotinib arm and 123 days in the sorafenib/placebo arm. In the sorafenib/erlotinib and sorafenib/placebo arms, the rates of treatment-emergent serious AEs (58.0% v 54.6%, respectively) and drug-related serious AEs (21.0% v 22.8%, respectively) were similar. AEs matched the known safety profiles of both agents, but rates of rash/desquamation, anorexia, and diarrhea were higher in the sorafenib/erlotinib arm, whereas rates of alopecia and hand-foot skin reaction were higher in the sorafenib/placebo arm. Withdrawal rates for AEs during cycles 1 to 3 were higher in the sorafenib/erlotinib arm.
Adding erlotinib to sorafenib did not improve survival in patients with advanced HCC.
在一项多中心、多国家、随机、III 期临床试验中，比较索拉非尼联合厄洛替尼或安慰剂治疗晚期肝细胞癌（HCC）患者的临床结局。
纳入 720 例未接受过系统治疗（N = 720）、Child-Pugh 分级为 A 级的晚期 HCC 患者，随机分为索拉非尼联合厄洛替尼（n = 362）或安慰剂（n = 358）组。主要终点为总生存期（OS）。
索拉非尼联合厄洛替尼组和索拉非尼联合安慰剂组的中位 OS 相似（分别为 9.5 个月和 8.5 个月，风险比 [HR]，0.929；P =.408），中位无进展生存期（PFS）也相似（分别为 3.2 个月和 4.0 个月，HR，1.135；P =.18）。与索拉非尼/安慰剂组相比，索拉非尼/厄洛替尼组的总缓解率（6.6% vs. 3.9%；P =.102）升高，疾病控制率（43.9% vs. 52.5%；P =.021）显著降低。索拉非尼治疗的中位持续时间在索拉非尼/厄洛替尼组为 86 天，在索拉非尼/安慰剂组为 123 天。在索拉非尼/厄洛替尼和索拉非尼/安慰剂组中，治疗相关严重不良事件（AE）发生率（分别为 58.0%和 54.6%）和药物相关严重 AE 发生率（分别为 21.0%和 22.8%）相似。AE 与两种药物的已知安全性特征相符，但索拉非尼/厄洛替尼组的皮疹/脱屑、厌食和腹泻发生率较高，而索拉非尼/安慰剂组的脱发和手足皮肤反应发生率较高。AE 导致的治疗周期 1-3 中停药率在索拉非尼/厄洛替尼组较高。
在晚期 HCC 患者中，索拉非尼联合厄洛替尼并未改善生存。
