Crizotinib Active in MET+ Papillary mRCC Type 1

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Crizotinib induces objective responses and long-lasting disease control in metastatic papillary renal cell carcinoma type 1.
Crizotinib induces objective responses and long-lasting disease control in metastatic papillary renal cell carcinoma type 1.

Crizotinib induces objective responses and long-lasting disease control in patients with metastatic papillary renal cell carcinoma type 1 (PRCC1) who harbor somatic MET mutation, according to findings presented at the American Academy for Cancer Research (AACR) Annual Meeting 2016.1

Because PRCC1 is associated with mutations of the MET gene, which encodes the MET tyrosine kinase receptor and leads to activation of this cancer-promoting pathway, researchers sought to evaluate the activity and safety of the ALK/ROS/MET inhibitor crizotinib in this patient population.

For the study, researchers enrolled 23 patients with advanced/metastatic PRCC1. All participants received crizotinib at a starting dose of 250 mg orally twice daily in 21-day cycles.

Results showed that among the 4 patients with MET mutation-positive disease, 2 achieved a confirmed partial response and 1 had stable disease. All 3 patients had long-lasting disease control. In contrast, none of the 13 patients with MET mutation-negative PRCC1 achieved a response. Treatment duration was short for all but 1 patient, who achieved long term stable disease.

There were also 6 patients with unknown mutational status. Of those, 2 achieved long-term control, potentially suggesting that they harbored other MET-activating mutations.

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The safety profile of crizotinib in this treatment setting has not yet been determined.

Crizotinib was initially approved by the U.S. Food and Drug Administration in 2011 for the treatment of patients with anaplastic lymphoma kinase (ALK) mutation-positive metastatic non-small cell lung cancer (NSCLC). It is also indicated for patients with metastatic NSCLC whose tumors are ROS1-positive.

Reference

  1. Schoffski P, Wozniak A, Escudier B, et al. Crizotinib achieves objective responses and long-lasting disease control in patients (pts) with metastatic papillary renal cell carcinoma type 1 (PRCC1) with somatic MET mutations. Oral presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.

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