Dr Rana McKay on Second-Line Treatment Options for Advanced RCC

Second-line therapies for renal cell carcinoma (RCC), or kidney cancer, are still evolving, said Rana R. McKay, MD, associate professor of Medicine and Urology, Moores Cancer Center, University of California San Diego.

AJMC®: What are some of the common second-line treatment options for patients with advanced RCC, including targeted therapies, immunotherapies, and chemotherapy?

McKay: The treatment options for patients in the second-line setting has been evolving because of a change in the way we treat patients in the frontline setting. We have moved away from vascular endothelial growth factor (VEGF) monotherapy frontline, to now [immunotherapy] IO combination therapy frontline and many of the trials that guided what to do in the second line, at least the large prospective trials, were largely done in patients having had received VEGF monotherapy frontline. The data are still evolving regarding what's the optimal second-line regimens to use in patients who have progression following immunotherapy and immunotherapy given alone or in combination with VEGF TKIs. The drugs that have demonstrated activity for post immunotherapy include cabozantinib; there's a subset analysis from the METEOR trial. There's a small number of patients that had received immunotherapy that study.

There was a study that looked at the combination of telaglenastat, which is a glutamine inhibitor, combined with cabozantinib versus cabozantinib alone. A large portion of patients who went on that study had received prior IO. The study was negative but that study demonstrated the activity of cabozantinib post IO. There is activity of lenvatinib post IO as well.

And other VEGF TKI post IO but the phase 3 data are lacking. The TIVO-3 study also looked at tivozanib post IO and post VEGF. the TIVO-3 study had a subset of patients who had received prior IO, so we do also have activity of that agent following immunotherapy treatment.

AJMC®: What are some of the factors that can influence the choice of second-line therapy in patients with advanced RCC, such as disease stage, patient age, and comorbidities and previous treatment regimens.

McKay: There's many factors to consider when selecting the optimal second-line therapy for a given patient. I think understanding what their risk factors are, their IMDC risk factors, understanding their sites of metastases, their burden of metastases, whether they're symptomatic or not symptomatic. How did they do on their first-line therapy? Did they do well for a prolonged period of time and had a response or did they rapidly progress on treatment and I think these decisions can help guide what to do. Additionally, I think histology matters whether they're clear cell, nonclear cell. I think we're moving into a field where we're doing more enhanced genomic profiling of these tumors. This is another opportunity to use such information to guide therapy selection.

AJMC®: How do you assess response to second-line therapies in patients with advanced RCC? And what criteria do you use to determine treatment success or failure?

McKay: Success of a second-line therapy is largely dependent on how a patient's feeling—are you improving their symptoms? Are you repeating scans and sharing there's disease stability and lack of progression on scans? And those are the 2 key parameters that are utilized to assess whether therapy is working.

AJMC®: What challenges are associated with selecting and administering second-line therapies for advanced RCC in patients who have received multiple prior treatments?

McKay: I think clinical trials are always a great option for patients. I think even the first-line setting, second-line setting at any line of therapy, it's really important to help patients get on clinical trials and understand how to sequence clinical trials into their repertoire of therapies that they have at their disposal. I think this is also another setting where I definitely integrate molecular sequencing to see if there are some unique changes within the tumor that could suggest that they would be a responder to specific sort of therapy.

AJMC®: What are you working on in RCC that you are excited to share?

McKay: We're working on a lot of excellent projects in RCC. There's a handful of clinical trials that we have currently ongoing asking specific questions about unmet needs in the field. There's patients with bone metastases and RCC continue to have very poor outcomes. And we've designed a study looking at ligand therapy with a cabozantinib in patients with bone metastases. The name of that study that we designed in the bone map patients is called the Radical Trial.

Additionally, the role of radiation therapy has been evolving.

In addition, we have been keen on investigating the role of radiotherapy in patients with advanced disease, especially as radiotherapy technologies have improved.

We have a trial called the SAMURAI trial that's being conducted through NRG, the National Radiation Oncology Group, testing the efficacy of radiation to the renal primary in patients receiving IO combination therapy in the frontline setting. I think these are going to be really critical studies to help advance the field forward and answer unmet questions in the field.