Scott S. Tykodi, MD, PhD, a physician with the Seattle Cancer Care Alliance, an associate professor within the Division of Medical Oncology at the University of Washington, and an associate professor of the Clinical Research Division, Fred Hutchinson Cancer Research Center, provides background to the phase 2 KEYNOTE-427 trial with pembrolizumab (Keytruda) in renal cell carcinoma (RCC).

KEYNOTE-427 is a single-arm frontline study of pembrolizumab monotherapy for advanced RCC,says Tykodi. Cohort A included patients with a clear-cell histology only, while cohort B included patients with non–clear cell disease, says Tykodi. Cohort A enrolled a total of 110 patients. The clinical outcomes have been presented previously and showed an objective response rate of 36%, which included 3 complete responses and a median progression-free survival of 7.1 months.

These are interesting data because this was the first study looking at monotherapy with an anti–PD-1 agent in kidney cancer, notes Tykodi. These results indicate that pembrolizumab is a highly effective drug, but it’simportant to recognize that the current FDA-approved frontline regimens are all doublets, such as PD-1 plus CTLA-4 blockade or PD-1/PD-L1 with a VEGF TKI. 

Now, investigators have taken the data set with well-established clinical end points, dug a bit deeper, and looked for biomarkers that might identify which patients are most likely to respond to treatment, explains Tykodi.This was a popular topic at the 

, and many similar attempts to look at the large clinical databases for biomarker discovery were made, notes Tykodi.

One of the techniques was taking the tumor tissue, conducting RNA sequencing, then clustering the gene expression into coherent pathways, and looking to see whether there is a signature of a biological pathway that is associated with the outcomes data, concludes Tykodi.

Videos

Scott S. Tykodi, MD, PhD, provides background to the phase 2 KEYNOTE-427 trial with pembrolizumab in renal cell carcinoma.

Dr. Tykodi on the KEYNOTE-427 Trial With Pembrolizumab in RCC

Scott S. Tykodi, MD, PhD, physician, Seattle Cancer Care Alliance, associate professor, Division of Medical Oncology, Clinical Research Division, University of Washington, Fred Hutchinson Cancer Research Center, discusses the clinical implications of the phase 2 KEYNOTE-427 trial in advanced renal cell carcinoma (RCC). 

, findings from the study showed promising antitumor activity with pembrolizumab (Keytruda) monotherapy as first-line therapy in patients with advanced RCC. 

These data represent a potential option for frail patients with advanced RCC who are ineligible to receive doublet therapy but may benefit from PD-1/PD-L1 inhibitors, explains Tykodi.

Pembrolizumab monotherapy has been evaluated in the adjuvant setting for patients with RCC following nephrectomy in the phase 3 KEYNOTE-564 trial. 

Although pembrolizumab monotherapy is not expected to receive an indication in the frontline setting in advanced RCC, it is approved in combination with axitinib (Inlyta) in this setting, Tykodi concludes.

Scott S. Tykodi, MD, PhD, discusses the clinical implications of the phase 2 KEYNOTE-427 trial in advanced renal cell carcinoma.  



Dr. Tykodi on the Clinical Implications of the KEYNOTE-427 Trial in Advanced RCC 

Scott S. Tykodi, MD, PhD, physician, Seattle Cancer Care Alliance, associate professor, Division of Medical Oncology, Clinical Research Division, University of Washington, Fred Hutchinson Cancer Research Center, discusses the efficacy of dual checkpoint blockade in renal cell carcinoma (RCC).

Most large studies evaluating dual checkpoint inhibitor blockade are fairly immature, explains Tykodi.

Currently, the phase 3 CheckMate-214 trial of nivolumab (Opdivo) in combination with ipilimumab (Yervoy) has the longest follow-up, says Tykodi. At 42 months, median overall survival was 47 months with the combination versus 26.6 months with sunitinib (Sutent) in patients with intermediate- and poor-risk advanced RCC.

Compared to other available treatments in this setting including TKIs and cytokine therapies, checkpoint inhibitors appear to show promising clinical activity in this patient population, concludes Tykodi.

Scott S. Tykodi, MD, PhD, discusses the efficacy of dual checkpoint blockade in renal cell carcinoma.



Scott S. Tykodi, MD, PhD

Articles

Dr. Tykodi on the KEYNOTE-427 Trial With Pembrolizumab in RCC

Dr. Tykodi on the Clinical Implications of the KEYNOTE-427 Trial in Advanced RCC

Dr. Tykodi on the Efficacy of Dual Checkpoint Blockade in RCC