Schnell Patrick, Bartlett Cynthia H, Solomon Benjamin J, Tassell Vanessa, Shaw Alice T, de Pas Tommaso, Lee Soo-Hyun, Lee Geon Kook, Tanaka Kaoru, Tan Weiwei, Tang Yiyun, Wilner Keith D, Safferman Allan, Han Ji-Youn
Pfizer Oncology, New York, New York.
Peter MacCallum Cancer Centre, Melbourne, Australia.
Cancer Med. 2015 Jun;4(6):887-96. doi: 10.1002/cam4.437. Epub 2015 Mar 10.
An apparent causal association between crizotinib treatment and renal cyst development emerged during clinical trials in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Serious adverse event (SAE) reports of renal cysts from a safety database of 1375 patients from four clinical trials were reviewed. A blinded, retrospective, independent radiologic review (IRR) was performed using scans from patients on study for ≥ 6 months in three clinical trials; risk factors for renal cyst development were assessed. Among 17 patients with renal cysts reported as SAEs, evidence of invasion into adjacent structures was noted in seven patients, with no evidence of malignancy found. These patients generally did not require dose reductions, none required permanent crizotinib discontinuation due to this AE, and most continued treatment with clinical benefit. In the blinded IRR, among 255 crizotinib-treated patients, 22%, 3%, and 2% had preexisting simple cysts, complex cysts, or both, respectively. At the 6-month tumor assessment, 9% of all patients had acquired new cysts, and 2% of patients with preexisting cysts had developed new cysts and enlargements (>50%) of preexisting simple cysts. Asians appeared to have an increased risk of developing new cysts on treatment; Koreans in particular had 5.18 times higher odds of developing cysts than non-Asians (95% confidence interval, 1.51-17.78; P = 0.05). Crizotinib treatment appears to be associated with an increased risk of development and progression of renal cysts in patients with ALK-positive NSCLC. While close monitoring is recommended, dosing modification was not generally necessary, allowing patients to remain on crizotinib treatment.
在间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）的临床试验期间，出现了克唑替尼治疗与肾囊肿形成之间明显的因果关联。我们回顾了来自四项临床试验的1375名患者安全数据库中关于肾囊肿的严重不良事件（SAE）报告。对三项临床试验中接受研究≥6个月的患者的扫描结果进行了一项盲法、回顾性、独立影像学审查（IRR）；评估了肾囊肿形成的危险因素。在报告为SAE的17例肾囊肿患者中，7例患者有侵犯相邻结构的证据，但未发现恶性证据。这些患者一般不需要降低剂量，没有患者因该不良事件而永久停用克唑替尼，并且大多数患者继续治疗并获得临床益处。在盲法IRR中，在255例接受克唑替尼治疗的患者中，分别有22%、3%和2%的患者有既往单纯囊肿、复杂性囊肿或两者皆有。在6个月的肿瘤评估时，所有患者中有9%出现了新囊肿，既往有囊肿的患者中有2%出现了新囊肿且既往单纯囊肿增大（>50%）。亚洲人在治疗期间出现新囊肿的风险似乎增加；尤其是韩国人发生囊肿的几率是非亚洲人的5.18倍（95%置信区间，1.51 - 17.78；P = 0.05）。克唑替尼治疗似乎与ALK阳性NSCLC患者肾囊肿形成和进展的风险增加有关。虽然建议密切监测，但一般不需要调整剂量，患者可继续接受克唑替尼治疗。
