Gore Martin E, Szczylik Cezary, Porta Camillo, Bracarda Sergio, Bjarnason Georg A, Oudard Stéphane, Hariharan Subramanian, Lee Se-Hoon, Haanen John, Castellano Daniel, Vrdoljak Eduard, Schöffski Patrick, Mainwaring Paul, Nieto Alejandra, Yuan Jinyu, Bukowski Ronald
Royal Marsden Hospital NHS Trust, London, UK.
Lancet Oncol. 2009 Aug;10(8):757-63. doi: 10.1016/S1470-2045(09)70162-7. Epub 2009 Jul 15.
Results from clinical trials have established sunitinib as a standard of care for first-line treatment of advanced or metastatic renal-cell carcinoma (RCC); however, many patients, particularly those with a poorer prognosis, do not meet inclusion criteria and little is known about the activity of sunitinib in these subgroups. The primary objective of this trial was to provide sunitinib on a compassionate-use basis to trial-ineligible patients with RCC from countries where regulatory approval had not been granted.
Previously treated and treatment-naive patients at least 18 years of age with metastatic RCC were eligible. All patients received open-label sunitinib 50 mg orally once daily on schedule 4-2 (4 weeks on treatment, 2 weeks off). Safety was assessed regularly, tumour measurements done per local practice, and survival data collected where possible. Analyses were done in the modified intention-to-treat (ITT) population, which consisted of all patients who received at least one dose of sunitinib. This study is registered with ClinicalTrials.gov, NCT00130897.
As of December, 2007, 4564 patients were enrolled in 52 countries. 4371 patients were included in the modified ITT population. This population included 321 (7%) patients with brain metastases, 582 (13%) with Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher, 588 (13%) non-clear-cell RCC, and 1418 (32%) aged 65 years or more. Patients received a median of five treatment cycles (range 1-25). Reasons for discontinuation included lack of efficacy (n=1168 [27%]) and adverse events (n=362 [8%]). The most common treatment-related adverse events were diarrhoea (n=1936 [44%]) and fatigue (n=1606 [37%]). The most common grade 3-4 adverse events were fatigue (n=344 [8%]) and thrombocytopenia (n=338 [8%]) with incidences of grade 3-4 adverse events similar across subgroups. In 3464 evaluable patients, the objective response rate (ORR) was 17% (n=603), with subgroup ORR as follows: brain metastases (26 of 213 [12%]), ECOG performance status 2 or higher (29 of 319 [9%]), non-clear-cell RCC (48 of 437 [11%]) and age 65 years or more (176 of 1056 [17%]). Median progression-free survival was 10.9 months (95% CI 10.3-11.2) and overall survival was 18.4 months (17.4-19.2).
In a broad population of patients with metastatic RCC, the safety profile of sunitinib 50 mg once-daily (initial dose) on schedule 4-2 was manageable and efficacy results were encouraging, particularly in subgroups associated with poor prognosis who are not usually entered into clinical trials.
Pfizer Inc.
临床试验结果已确立舒尼替尼为晚期或转移性肾细胞癌（RCC）一线治疗的标准疗法；然而，许多患者，尤其是预后较差的患者，不符合纳入标准，且对于舒尼替尼在这些亚组患者中的活性了解甚少。本试验的主要目的是在同情用药的基础上，为来自尚未获得监管批准国家的不符合试验条件的RCC患者提供舒尼替尼。
年龄至少18岁、既往接受过治疗或未接受过治疗的转移性RCC患者符合条件。所有患者均接受开放标签的舒尼替尼，50mg口服，每日一次，采用4-2方案（治疗4周，停药2周）。定期评估安全性，根据当地实际情况进行肿瘤测量，并尽可能收集生存数据。分析在改良意向性治疗（ITT）人群中进行，该人群包括所有接受过至少一剂舒尼替尼的患者。本研究已在ClinicalTrials.gov注册，编号为NCT00130897。
截至2007年12月，52个国家的4564例患者入组。4371例患者纳入改良ITT人群。该人群包括321例（7%）脑转移患者、582例（13%）东部肿瘤协作组（ECOG）体能状态为2或更高的患者、588例（13%）非透明细胞RCC患者以及1418例（32%）年龄在65岁及以上的患者。患者接受治疗的中位周期数为5个周期（范围1-25个周期）。停药原因包括缺乏疗效（n=1168[27%]）和不良事件（n=362[8%]）。最常见的治疗相关不良事件为腹泻（n=1936[44%]）和疲劳（n=1606[37%]）。最常见的3-4级不良事件为疲劳（n=344[8%]）和血小板减少（n=338[8%]），各亚组中3-4级不良事件的发生率相似。在3464例可评估患者中，客观缓解率（ORR）为17%（n=603），各亚组的ORR如下：脑转移患者（213例中的26例[12%]）、ECOG体能状态为2或更高的患者（319例中的29例[9%]）、非透明细胞RCC患者（437例中的48例[11%]）以及年龄在65岁及以上的患者（1056例中的176例[17%]）。中位无进展生存期为10.9个月（95%CI 10.3-11.2），总生存期为18.4个月（17.4-19.2）。
在广泛的转移性RCC患者群体中，每日一次（初始剂量）50mg舒尼替尼采用4-2方案的安全性是可控的，疗效结果令人鼓舞，尤其是在通常不纳入临床试验的预后较差亚组患者中。
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