In the end, it is a matter of experience. There are well-established treatment guidelines for some of these adverse effects. Most of these patients do well with steroids. The need to add additional immune-suppressive agents is around 4%. Many patients do well with steroids from 4 to 6 weeks.
Can you discuss the next line of therapy for patients who progress on the combination?
Other PD-1/PD-L1 inhibitors will likely work in that space if a patient progresses on nivolumab and ipilimumab. The mechanisms of action are too similar. In that case, we are back to our work forces that we have been employing for the last 10 to 11 years, which are the TKIs and the VEGF pathway inhibitors. We have a wide spectrum of agents to choose from. For example, we know that using axitinib (Inlyta) in this particular space is safe. It is also one of the TKIs that is well combinable with other immunotherapies.
If a patient has some intermediate- or poor-risk features as well as a large tumor burden, then perhaps one should go with cabozantinib (Cabometyx), which is one of the more broadly acting TKIs. The art of oncology is choosing some new agents but, essentially, it is back to VEGF TKIs.
Hopefully, the patients can do well on these agents and participate in clinical trials—or look forward to other immunotherapy combinations that are coming up in the future.
What are the next steps with treatments and where do you hope to be in the next 5 to 10 years with this landscape?
Quite frankly, we are trying to make sense and to develop a rational approach for the different agents that are coming into clinical development. The class of checkpoint inhibitors is expanding. We need to revisit the role of vaccination therapy with combinations of immune checkpoints in kidney cancer that can be mutation based. That will be a large wave of clinical trials and studies. There is lots of work to be done. We are all looking forward to other classes that are in development.
There is a phase III clinical trial that is investigating the frontline combination of epacadostat and pembrolizumab (Keytruda) versus sunitinib. There are several agents that are being tested in pivotal trials or in earlier development trials that we can hopefully get access to in the future.
Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: Efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract LBA5.