Dr. Choueiri on the Subgroup Analysis of the JAVELIN Renal 101 Trial in RCC

Toni Choueiri, MD, director, Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, senior physician, Dana-Farber Cancer Institute, and Jerome and Nancy Kohlberg Associate Professor of Medicine, Harvard Medical School, discusses findings from the subgroup analysis of the phase III JAVELIN Renal 101 trial in advanced renal cell carcinoma (RCC).

In the trial, the frontline combination of avelumab (Bavencio) and axitinib (Inlyta) resulted in a 31% reduction in disease progression or death in patients with advanced RCC compared with sunitinib (Sutent) monotherapy. A subgroup analysis led by Choueiri indicated that patients on the combination arm benefited irrespective of PD-L1 expression, whereas PD-L1—positive patients did worse with sunitinib, mirroring prior findings. Further analysis revealed that a high CD8 count indicated a greater likelihood of benefit in the combination arm, whereas a low CD8 count indicated a greater likelihood of benefit in the sunitinib arm.

Investigators then set out to analyze over 4,000 genes; of these genes, 306 were found to play a role in immune response. Ultimately 26 genes were identified as having a key immunologic role in RCC from which investigators created a signature to identify potential responders. Subsequent application of the signature helped them to identify patients who had a prolonged progression-free survival with the combination. These findings were validated from the phase Ib trial, says Choueiri. Finally, whole exome sequencing revealed certain genes that were associated with a better response to either the combination or monotherapy. Although these findings require further validation, they set the stage for extrapolation to other combinations of immunotherapy and VEGF TKIs, concludes Choueiri.