Ulka N. Vaishampayan, MBBS, FAB, director of the Phase I program at the Rogel Cancer Center and a professor of internal medicine at the University of Michigan, discusses the expanding role of TKI/immunotherapy combinations in metastatic renal cell carcinoma (mRCC). 

Several ​VEGF TKI/immunotherapy combinations have established efficacy in metastatic RCC, says Vaishampayan.

Inlyta) plus pembrolizumab (Keytruda) and axitinib plus avelumab (Bavencio) are approved for the treatment of patients with mRCC, says Vaishampayan. Both regimens have shown significant improvement​s in overall response rate (ORR) and progression-free survival (PFS) compared with sunitinib 

Additionally, findings from the phase 3 KEYNOTE-426 trial demonstrated an overall survival (OS) benefit with the combination of axitinib and pembrolizumab​.

Notably, results from the phase 3 CheckMate​-9ER trial, which were presented during the 

, demonstrated superiority with the combination of nivolumab (Opdivo) and cabozantinib (Cabometyx) ​vs sunitinib in terms of PFS, OS and ORR ​for the first-line treatment of patients with ​advanced RCC. 

In fact, the median PFS was doubled from 8​.3 months with sunitinib to 16.6 months with the combination, Vaishampayan concludes.

Videos

Ulka N. Vaishampayan, MBBS, FAB, discusses the expanding role of TKI/immunotherapy combinations in metastatic renal cell carcinoma. 

Dr. Vaishampayan on the Expanding Role of TKI/Immunotherapy Combinations in mRCC

Ulka N. Vaishampayan, MBBS, FAB, director of the Phase I program at the Rogel Cancer Center and a professor of internal medicine at the University of Michigan, discusses the safety profiles of tivozanib (Fotivda) versus sorafenib (Nexavar) in advanced renal cell carcinoma.

In terms of efficacy, tivozanib has shown to be superior in progression-free survival compared with sorafenib, says Vaishampayan. However, a statistically significant benefit in overall survival had not been observed with tivozanib over sorafenib. 

When choosing between the agents, the toxicity profiles of both agents have to be considered, as well as their mechanisms of action. Sorafenib has a RAF kinase inhibitor activity, as well as VEGF TKI activity, whereas tivozanib is a preferential VEGF TKI inhibitor only with selective activity against VEGF.

The toxicity profile of sorafenib seems to reflect a higher risk of hand-foot syndrome and skin rashes as compared with tivozanib. The risk of hypertension and other toxicities that are VEGF-related appear to be comparable between the agents, concludes Vaishampayan.

Ulka N. Vaishampayan, MBBS, FAB, discusses the safety of tivozanib versus sorafenib in advanced renal cell carcinoma.

Dr. Vaishampayan on the Safety of Tivozanib Versus Sorafenib in RCC

Ulka N. Vaishampayan, MBBS, FAB, director of the Phase I program at the Rogel Cancer Center and a professor of internal medicine at the University of Michigan, discusses the potential of tivozanib (Fotivda) in advanced renal cell carcinoma (RCC).

At present, tivozanib is not approved for use in the United States for patients with advanced RCC, although it has been approved in Europe; it is used as a single-agent VEGF TKI in this patient population, says Vaishampayan. In the United States, given the results of the phase 3 TIVO-3 trial, tivozanib could be a reasonable third-line option to consider for patients who have already received both VEGF TKI and immune-based regimens, adds Vaishampayan.

Tivozanib appears to prolong progressing-free survival, is relatively well-tolerated, and may provide patients with an additional efficacy benefit in the pretreated setting, concludes Vaishampayan.

Ulka N. Vaishampayan, MBBS, FAB, discusses the potential of tivozanib in advanced renal cell carcinoma.

Dr. Vaishampayan on the Potential of Tivozanib in Advanced RCC

Ulka N. Vaishampayan, MBBS, FAB, director of the Phase I program at the Rogel Cancer Center and a professor of internal medicine at the University of Michigan, discusses the need to develop novel therapies for patients with metastatic renal cell carcinoma (mRCC).

About 50% to 60% of patients with mRCC do not derive a response to immunotherapy or are considered refractory to immunotherapy, Vaishampayan says.

Although these patients may be salvaged with VEGF TKIs, the majority of patients are not being cured of their disease, explains Vaishampayan. 

As such, developing novel drugs and targets is critically important to continue moving the field of advanced RCC forward, concludes Vaishampayan.

Ulka N. Vaishampayan, MBBS, FAB, discusses the need to develop novel therapies for patients with metastatic renal cell carcinoma.



Dr. Vaishampayan on the Need to Develop Novel Therapies in mRCC 

Ulka N. Vaishampayan, MBBS, FAB, director of the Phase I program at the Rogel Cancer Center and a professor of internal medicine at the University of Michigan, discusses the benefit of axitinib (Inlyta) and pembrolizumab (Keytruda) in advanced renal cell carcinoma (RCC).

Updated results from the phase 3 KEYNOTE-426 trial showed that at 24 months of follow-up, patients who were given axitinib/pembrolizumab still experienced an improvement in survival, says Vaishampayan. The 2-year overall survival rate for patients who received sunitinib (Sutent) was 66% versus 74% of those who received the combination. The difference in benefit continues to be statistically significant, and as such, the immunotherapy-based regimen is still considered as the frontline therapy of choice for patients with RCC. adds Vaishampayan.

However, when looking at the International Metastatic RCC Database risk criteria, the favorable-risk subgroup did not show a benefit with axitinib/pembrolizumab; both arms experienced relatively similar outcomes. In the intermediate- and poor-risk subgroup, the difference remained and favored the axitinib/pembrolizumab regimen, concludes Vaishampayan.

Ulka N. Vaishampayan, MBBS, FAB, discusses the benefit of axitinib and pembrolizumab in advanced renal cell carcinoma.

Ulka N. Vaishampayan, MBBS, FAB

Articles

Dr. Vaishampayan on the Expanding Role of TKI/Immunotherapy Combinations in mRCC

Dr. Vaishampayan on the Safety of Tivozanib Versus Sorafenib in RCC

Dr. Vaishampayan on the Potential of Tivozanib in Advanced RCC

Dr. Vaishampayan on the Need to Develop Novel Therapies in mRCC

Dr. Vaishampayan on Axitinib Plus Pembrolizumab in Advanced RCC