Novel MET Inhibitor Shows Encouraging Results in Papillary Renal Cell Carcinoma

Toni K. Choueiri, MD

Patients with MET-driven papillary renal cell carcinoma (RCC) experienced better efficacy and safety with savolitinib versus the current standard of care, according to research presented at the 2020 ASCO Virtual Scientific Program.

Patients taking savolitinib, a highly selective MET-tyrosine kinase inhibitor, also experienced fewer grade 3 or 4 adverse events (AEs) while requiring fewer dose modifications than sunitinib (Sutent), which performed more poorly than the external retrospective data anticipated.

“Although patient numbers and follow-up were limited, savolitinib demonstrated encouraging efficacy and an improved safety profile versus sunitinib,” said lead study author Toni K Choueiri, MD, director, Lank Center for Genitourinary Oncology and the Kidney Cancer Center, Dana-Farber Cancer Institute, in his presentation of the data.

A total of 254 patients were screened for treatment, but only 60 were randomized because the MET-driven alteration was not detected in most of the population (n = 181). Median age for the savolitinib group was 60 years compared to 65 years for the sunitinib group. Overall, 33 patients were randomized to savolitinib and 27 patients to sunitinib.

Median progression-free survival (PFS) for patients in the savolitinib group was 7.0 months (95% CI, 2.8 to not reached) compared to 5.6 months (95% CI, 4.1-6.9) for patients in the sunitinib group (HR, 0.71; 95% CI, 0.37-1.36; P = .313). More, overall survival (OS) was not reached for savolitinib and was 13.2 months for sunitinib (HR, 0.51; 95% CI, 0.21-1.17; P = .110).

Grade 3 or 4 AEs occurred in 42% of patients in the savolitinib group compared to 81% in the sunitinib group. The most common AEs for the savolitinib group were edema peripheral (33%), alanine aminotransferase increase (24%), aspartate aminotransferase increase (24%), and dyspnea (21%). For sunitinib, the most common AEs were anemia (44%), nausea (33%), and decreased appetite (30%).

The primary endpoint of the research PFS by blinded independent center review. Secondary endpoints were OS, overall response rate by blinded independent center review, safety, and health-related quality of life.

“There’s a subset of papillary RCC that are MET-driven, suggesting perhaps that MET inhibition may be an appropriate targeted treatment approach,” explained Choueiri. “MET has been found to be associated with major chromosome-level alteration in papillary RCC.”

At data cutoff, none of the responding patients in the savolitinib group (n = 9) saw disease progression. However, 1 of the 2 responding patients in the sunitinib group had disease progression. Because of the low response rate, it was not possible to calculate the median duration of response among the population.

Papillary renal cell carcinoma accounts for approximately 15% of all RCC, making it the most common type of non-clear cell RCC.

While no definitive conclusions could be drawn from the data due to a number of factors including a small sample size and early termination, the researchers suggest further studies to examine the viability of savolitinib.

“Early termination of recruitment precludes definitive conclusions from being drawn due to the small dataset,” explained Choueiri. “However, based on the emerging data, further investigation of savolitinib as a treatment option for MET-driven [papillary] RCC is warranted.”

_Reference:

_{Choueiri TK, Heng DYC, Lee J, et al. SAVOIR: A phase III study of savolitinib versus sunitinib in pts with MET-driven papillary renal cell carcinoma (PRCC). Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 5002.}