Dr. Hsieh on Patient Characterization From RECORD-3 Study in Metastatic RCC

James J. Hsieh, MD, medical oncologist, physician-scientist, Memorial Sloan Kettering Cancer Center, discusses overall survival results in the RECORD-3 study based on 3 distinct clear cell metastatic renal cell carcinoma molecular subgroups.

RECORD-3 is a randomized large phase III study of 471 untreated patients looking at sunitinib (Sutent) or everolimius (Afinitor) as first-line treatment, Hsieh explains. Patients then undergo crossover upon disease progression. The progression-free survival outcomes favored sunitinib over everolimus; however, the treatment outcomes were heterogenous. This suggested that this is a heterogenous tumor group and researchers sought to identify what underlies the heterogeneity.

Researchers collected 220 tumor samples from the RECORD-3 patients who were of the clear cell subtype. Next-generation sequencing analyses were done to compare the tumor mutations with treatment response. Findings showed that the KDM5C mutation, which are likely to occur in males, were associated with exceptional responses with sunitinib, suggesting that this is a biomarker that will lead to long-term responses with this therapy.

However, PBRM1 and BAP1 mutations are those that are found to be mutually exclusive, Hsieh says. Patients who harbor these mutations are found to be high-risk and do poorly on treatment with everolimus. They do respond to sunitinib, however.