Ajjai Shivaram Alva, MBBS, an associate professor at the University of Michigan, discusses the shift toward combination therapy in metastatic renal cell carcinoma (mRCC).

The role of combination therapy has grown significantly in mRCC, explains Alva. As such, the utility of monotherapy in this space is diminishing.

By combining TKIs and checkpoint inhibitors, patients get the benefit of dual VEGF and PD-1/PD-L1 blockade, says Alva. Historically, both classes of agents have demonstrated activity in mRCC.

Going forward, the question of what treatment to give patients who progress on a TKI/immunotherapy combination needs to be answered, Alva says.

Novel classes of agents including metabolic inhibitors, glutamine inhibitors, arginase inhibitors, and HIF-1α inhibitors may have a role in the second-line setting, concludes Alva.

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Ajjai Shivaram Alva, MBBS, discusses the shift toward combination therapy versus monotherapy in metastatic renal cell carcinoma.

Dr. Alva on the Shift Toward Combination Therapy in mRCC

Ajjai Shivaram Alva, MBBS, an associate professor at the University of Michigan, discusses the results of the CABOSUN trial in renal cell carcinoma (RCC).

The randomized, phase II CABOSUN trial compared the multikinase inhibitor cabozantinib (Cabometyx) with sunitinib (Sutent) as a frontline treatment for patients with advanced RCC, explains Alva. The study, which had a primary endpoint of progression-free survival (PFS) by investigator assessment, demonstrated that cabozantinib is superior to sunitinib in patients with intermediate- or poor-risk RCC by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria, says Alva.

The CABOSUN trial has been validated by independent observers and assessments, continuing to show that cabozantinib, in terms of PFS and response rate, is a superior choice over sunitinib in patients with intermediate- or poor-risk RCC by IMDC criteria, concludes Alva.

Ajjai Shivaram Alva, MBBS, discusses the results of the CABOSUN trial in renal cell carcinoma.

Dr. Alva on Results of the CABOSUN Trial in RCC

Ajjai Shivaram Alva, MBBS, an associate professor at the University of Michigan, discusses TKI monotherapy and in combination with immunotherapy for patients with renal cell carcinoma (RCC).

TKIs have a continuing role in RCC therapy, either as a single agent for patients with favorable-risk disease in which TKIs appear superior to immunotherapy, or in combination with immunotherapy, explains Alva. The FDA approved 2 combinations for frontline RCC therapy: axitinib (Inlyta) plus avelumab (Bavencio) and axitinib plus pembrolizumab (Keytruda).

There are a few other combinations that are expected to read out soon, including lenvatinib (Lenvima) plus pembrolizumab and cabozantinib (Cabometyx) plus nivolumab (Opdivo), says Alva. TKI combinations for intermediate- and poor-risk patients are likely going to evolve in the upcoming years, concludes Alva.

Ajjai Shivaram Alva, MBBS, discusses TKI monotherapy and in combination with immunotherapy for patients with renal cell carcinoma.

Dr. Alva on TKI Monotherapy and Combinations for RCC

Ajjai Shivaram Alva, MBBS, an associate professor at the University of Michigan, discusses class-specific toxicities of TKIs in metastatic renal cell carcinoma (mRCC). 

Adverse events such as hypertension, rashes on the hands and feet, cardiac toxicity, gastrointestinal (GI) toxicities such as diarrhea and mucositis, dysphonia, transaminitis, and liver toxicity result from the drug’s mechanism of action, says Alva. The frequency of these events vary with each drug, but by and large, they are shared with the class of VEGF TKIs.

For example, tivozanib (Fotivda) can cause more dysphonia and axitinib (Inlyta) can cause more diarrhea. Additionally, sunitinib (Sutent) can cause more diarrhea and other GI toxicities. These drugs are also given on different schedules. For example, sunitinib is given every 4 weeks with 2 weeks off, whereas axitinib is a short-acting drug that’s given twice daily, explains Alva. Moreover, the starting dose of axitinib can be adjusted as necessary. Other TKIs are given once daily.

Ajjai Shivaram Alva, MBBS, discusses class-specific toxicities of TKIs in renal cell carcinoma.

Ajjai Shivaram Alva, MBBS

Articles

Dr. Alva on the Shift Toward Combination Therapy in mRCC

Dr. Alva on Results of the CABOSUN Trial in RCC

Dr. Alva on TKI Monotherapy and Combinations for RCC

Dr. Alva on the Toxicity Profiles of TKIs in RCC