Novel Combination Therapies Under Investigation in mRCC

Transcript:Thomas E. Hutson, DO, PharmD: The rationale for combining atezolizumab and bevacizumab is the same rationale for combining a VEGF inhibitor with immunotherapy. Bevacizumab is an intravenously available antibody against VEGF. There are some practical advantages to giving 2 intravenous therapies to a patient, to have them avoid taking an oral therapy at home. There’s nothing else more notable than that, as far as why they work. I think it has been one of the first reported combinations that really proves the principle that VEGF inhibition with immunotherapy can potentially raise efficacy and accomplish what we need it to. It’s unclear to me whether the results in that population—good- and intermediate-risk—make that combination unique to that setting or whether we will see the agents that we’ve already studied, ipilimumab/nivolumab and cabozantinib, which have shown benefit in the intermediate- and poor-risk patients, translate into that same space. I’ve seen nothing, and I’m aware of no underlying biology that would suggest that there should be a difference between the different prognostic groups.

The million-dollar question is whether or not the combination of atezolizumab and bevacizumab, if it received regulatory approval, would be given or uptaken in community oncology practice. It’s unclear to me whether or not that will happen. I think there are several factors involved with that—the price of the medication, chair time, and so many other extraneous factors that are involved. Also, cost to the patient is going to be important.

Chung-Han Lee, MD, PhD: The combination of an anti—PD-1 with an IDO inhibitor has been of great interest within the immune-oncology community. This is based off the role of kynurenine as an oncometabolite that suppresses T-cell activation. Tryptophan is metabolized to kynurenine by the enzyme IDO. Inhibitors of IDO are thought to enhance T-cell activation. This has been studied in multiple malignancies, including the originally proposed phase III clinical trial of epacadostat plus pembrolizumab for metastatic renal cell carcinoma, randomized against sunitinib. However, based off the recent results presented within melanoma, the culmination of pembrolizumab plus epacadostat didn’t reach its primary endpoints. Therefore, there has been a bit of a pause regarding what the role of IDO inhibition will end up being in combination with PD-1 inhibitors.

Transcript Edited for Clarity.