Savolitinib, a highly selective inhibitor of c-Met receptor tyrosine kinase, improved progression-free survival in a small portion of patients with MET-driven advanced renal papillary cell cancer.

The molecule, being developed by Hutchison China MediTech Limited and AstraZeneca, extended progression-free survival by about 5 months in these patients, compared with those whose tumors were not MET driven (6.2 vs. 1.4 months, respectively), reported Toni Choueiri, MD, and his colleagues (J Clin Oncol 2017. doi: 10.1200/JCO.2017.72.2967).

The response, however, was limited. Only eight of the patients with MET-driven tumors (18%) experienced a confirmed partial response. Non-MET tumors did not respond, wrote Dr. Choueiri of Dana-Farber Cancer Institute, Boston, and his coauthors.

Of 109 patients in the phase II study, 44 (40%) had MET-driven disease. The cancer was MET independent in 46 (42%); MET status was unknown in the remainder.

Half of those with MET-driven tumors experienced stable disease, and 61% experienced tumor shrinkage ranging from 0.7% to 66%. Tumor shrinkage occurred in 20% of those with MET-independent tumors. These also responded less vigorously (shrinkage 0.5%-20%).

Of the eight patients exhibiting a partial response, six were still responding to treatment at the study’s end, with response ranging from 2 to 16 months. Two patients experienced progressive disease after 1.8 and 2.8 months. By the end of the study, disease progression had occurred in 75% of the MET-driven cases, 96% of the MET-independent cases, and 74% of cases whose MET status was unknown.

“These results confirm that savolitinib … holds promise as a personalized treatment for patients with metastatic MET-driven papillary renal cell carcinoma,” the investigators wrote. The data also support the June launch of the phase III SAVOIR trial, they noted.

SAVOIR will enroll about 180 patients with MET-driven renal papillary cancer confirmed by a next-generation molecular sequencing developed by the companies for savolitinib response. Patients will be randomized to continuous treatment with savolitinib 600 mg orally, once daily, or intermittent treatment with sunitinib 50 mg orally once daily (4 weeks on/2 weeks off), on a 6-week cycle.

Dr. Choueiri has been a consultant for and received research funding from numerous pharmaceutical companies, including AstraZeneca.

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