Papillary Renal Cell Carcinomas May Respond to Crizotinib
Patients with PRCC1 frequently show MET mutations. Crizotinib, a dual inhibitor of MET and ALK, has shown promising activity in MET-altered cancers.
|The following article features coverage from the 2018 Genitourinary Cancers Symposium. Click here to read more of Cancer Therapy Advisor's conference coverage.|
Crizotinib may improve outcomes among patients with MET-positive papillary renal cell carcinoma type 1 (PRCC1), according to research being presented at the 2018 Genitourinary Cancers Symposium in San Francisco, California.1
Patients with PRCC1 frequently show MET mutations. Crizotinib, a dual inhibitor of MET and ALK, has shown promising activity in MET-altered cancers. For this phase 2 study (ClinicalTrials.gov Identifier: NCT01524926), researchers evaluated the safety and efficacy of crizotinib in patients with MET-positive or -negative advanced/metastatic PRCC1. The primary endpoint was objective response rate (ORR).
Of 41 enrolled patients, 23 received crizotinib 250 mg twice daily; 4 had MET-positive disease, 16 had MET-negative disease, and 3 had unknown MET status.
Two patients with MET-positive PRCC1 had a partial response and 1 had stable disease, conferring an ORR of 50%. The partial response durations were 666 and 1138 days; the 1-year progression-free survival and overall rates were each 75%.
Among patients with MET-negative disease, 1 had a partial response that lasted at least 300 days; 11 had stable disease (ORR, 6.3%). The 1-year progression-free survival and overall survival rates were 27.3% and 71.8%, respectively.
Two of the 3 patients with unknown MET status had a partial response or stable disease.
Edema and fatigue were noted in nearly half of patients (47.8% each). Other treatment-related adverse events included nausea (39.1%), diarrhea (39.1%), and blurred vision (34.8%).
The authors concluded that crizotinib “is active and well tolerated in advanced, metastatic PRCC1, achieving objective responses and long-lasting disease control in pts with MET mutations or amplification. Sporadic, durable responses are also seen in [MET-negative or -unknown] cases, suggesting the presence of other alterations of MET or alternative pathways.”
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- Schoffski P, Wozniak A, Escudier B, et al. Effect of crizotinib on disease control in patient with advanced papillary renal cell carcinoma type 1 with MET mutations or amplification: final results of EORTC 90101 CREATE. Oral presentation at: 2018 Genitourinary Cancers Symposium; February 8-10, 2018; San Francisco, CA.