Dr. Rini on Managing the Toxicity of Pembrolizumab Plus Axitinib in mRCC

Brian I. Rini, MD, professor of medicine, Cleveland Clinic, discusses managing the toxicity of pembrolizumab (Keytruda) plus axitinib (Inlyta) in patients with metastatic renal cell carcinoma (mRCC).

Combining 2 drugs will typically result in more toxic than a monotherapy, especially if it is 2 different classes of drugs. Fortunately, Rini notes, the PD-1 inhibitor pembrolizumab and the VEGF TKI axitinib are fairly well tolerated on their own. Axitinib is one of the better tolerated TKIs, with diarrhea, fatigue, and high blood pressure among the most common side effects. Pembrolizumab is associated with immune-related adverse events, but it is generally a tolerable agent.

In the phase III KEYNOTE-426 trial, the combination resulted in expected toxicities, Rini says. When one looks at the combination of ipilimumab (Yervoy) plus nivolumab (Opdivo), for example, there is a lot of inflammatory toxicity upfront. With pembrolizumab plus axitinib, the side effects are more drawn out. In April 2019, the FDA approved pembrolizumab plus axitinib for the frontline treatment of patients with mRCC based on the results of the KEYNOTE-426 trial.