Food and Drug Administration, White Oak Campus, 10903 New Hampshire Avenue, Building 22, Room 1243, Silver Spring, Maryland 20993-0002, USA.
Oncologist. 2012;17(8):1108-13. doi: 10.1634/theoncologist.2012-0044. Epub 2012 Jul 26.
On May 20, 2011, the U.S. Food and Drug Administration (FDA) approved sunitinib malate capsules (Sutent®; Pfizer, Inc., New York) for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs) in patients with unresectable locally advanced or metastatic disease. In a phase III randomized trial, 171 patients received either sunitinib (37.5 mg) or placebo once daily. The progression-free survival (PFS) interval was the primary efficacy endpoint. Secondary endpoints included the overall survival (OS) time, objective response rate (ORR), patient-reported outcomes, and safety. Based on early results favoring sunitinib, the independent data monitoring committee recommended trial termination prior to the prespecified interim analysis. This premature analysis may have led to an overestimate of the treatment effect. In the FDA analysis of investigator-assessed PFS times, the median values for the sunitinib and placebo arms were 10.2 months and 5.4 months, respectively. The ORRs were 9.3% and 0% in the sunitinib and placebo arms, respectively. The OS data were not mature at the time of approval and were confounded by 69% crossover. Common adverse reactions in patients receiving sunitinib included diarrhea, nausea, asthenia, fatigue, neutropenia, hypertension, and palmar-plantar erythrodysesthesia syndrome. Two patients on sunitinib died as a result of cardiac failure. The Oncologic Drugs Advisory Committee voted eight to two that, despite residual uncertainty about the magnitude of the PFS effect because of early trial termination, sunitinib demonstrated a favorable benefit-risk profile in pNET patients. The FDA concurred with the committee's assessment and granted sunitinib regular approval for this rare malignancy with few available therapies.
2011 年 5 月 20 日，美国食品和药物管理局（FDA）批准苹果酸舒尼替尼胶囊（Sutent®；辉瑞公司，纽约）用于治疗无法切除的局部晚期或转移性疾病患者的进行性、分化良好的胰腺神经内分泌肿瘤（pNET）。在一项 III 期随机试验中，171 名患者接受舒尼替尼（37.5mg）或安慰剂，每日一次。无进展生存期（PFS）是主要疗效终点。次要终点包括总生存期（OS）时间、客观缓解率（ORR）、患者报告的结果和安全性。基于早期有利于舒尼替尼的结果，独立数据监测委员会建议在预定的中期分析之前终止试验。这种过早的分析可能导致治疗效果的高估。在 FDA 对研究者评估的 PFS 时间的分析中，舒尼替尼组和安慰剂组的中位值分别为 10.2 个月和 5.4 个月。舒尼替尼组和安慰剂组的 ORR 分别为 9.3%和 0%。批准时 OS 数据不成熟，并且受到 69%交叉的影响。接受舒尼替尼治疗的患者常见不良反应包括腹泻、恶心、乏力、疲劳、中性粒细胞减少症、高血压和掌跖红细胞感觉不良综合征。两名接受舒尼替尼治疗的患者因心力衰竭死亡。肿瘤药物咨询委员会以八票对两票投票认为，尽管由于试验提前终止，对 PFS 效果的幅度仍存在不确定性，但舒尼替尼在 pNET 患者中表现出有利的风险效益比。FDA 同意委员会的评估，并批准舒尼替尼用于这种罕见的恶性肿瘤，因为这种恶性肿瘤的治疗方法很少。
