Complex renal cysts associated with crizotinib treatment

Abstract

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.

Development of Aseptic Renal Abscess in a Patient with Non-Small-Cell Lung Cancer with ALK Translocation during Crizotinib Treatment

“…Schnell et al [12] described only one patient of 17 with renal abscess [12]. They did not report any pathologic agent in this case.…”

“…In his analysis, 3 patients had to have dose reduced, the others were kept on regular doses without harm. Only one patient had to suspend treatment due to disease progression [12]. Other case report of a patient in Japan also showed spontaneous regression of a complex renal cyst [15].…”

“…Crizotinib increases the risk of renal cysts development and also increases pre-existing cystic lesions [12] [14].…”

“…In a retrospective analysis, among 1205 patients who received Crizotinib in the two largest Crizotinib clinical trials (PROFILE 1005 [11] and PROFILE 1007 [9]), 24 patients (2%) had adverse effects of treatment-related renal cysts [12]. In four clinical trials, 17 patients had renal cysts reported as serious adverse event [12].…”

“…Seventeen patients had severe side effects related to complex renal cysts, such as invasion of adjacent structures [12].…”