title: 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.
authors.affiliation: Pfizer Oncology, New York, New York.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schnell
authors.affiliation: Pfizer Oncology, New York, New York.
authors.forename: Cynthia H
authors.initials: CH
authors.lastname: Bartlett
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Solomon
authors.affiliation: Pfizer Oncology, La Jolla, California.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tassell
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Alice T
authors.initials: AT
authors.lastname: Shaw
authors.affiliation: European Institute of Oncology, Milan, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: de Pas
authors.affiliation: National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.affiliation: Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Pfizer Oncology, La Jolla, California.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Tan
authors.affiliation: Pfizer Oncology, La Jolla, California.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Pfizer Oncology, La Jolla, California.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Wilner
authors.affiliation: Pfizer Oncology, New York, New York.
authors.forename: Allan
authors.initials: A
authors.lastname: Safferman
authors.affiliation: National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077547:Crizotinib; D005260:Female; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000139:chemically induced*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011720:Pyrazoles / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib
keywords: Crizotinib; NSCLC; independent radiologic review; renal cysts; risk factors