Papillary Renal Cell Carcinomas May Respond to Crizotinib

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Patients with PRCC1 frequently show MET mutations. Crizotinib, a dual inhibitor of MET and ALK, has shown promising activity in MET-altered cancers.
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.”

Read more of Cancer Therapy Advisor's coverage of the 2018 Genitourinary Cancers Symposium by visiting the conference page.

Reference

  1. 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.

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