Subcutaneous Immunotherapy Options Available for Genitourinary Cancer

The panel reviews the clinical data behind subcutaneous pembrolizumab and nivolumab, comparing efficacy and pharmacokinetics to their IV counterparts, and shares early clinical impressions of introducing these formulations into practice.

Jeff Yorio, MD: Hi everybody. Welcome back for our second chapter of our series, which is Subcutaneous Immunotherapy for Genitourinary Cancers. This chapter is going to focus on subcutaneous immunotherapy options available for genitourinary cancers. My name is Dr Jeff Yorio. I'm a medical oncologist at Texas Oncology in Austin, and I serve as the site research leader for Central Texas for Texas Oncology and Sarah Cannon Research Institute, and also serve as an executive member of the Genitourinary Cancer Research Board for Sarah Cannon Research Institute. 

I have with me a great group of people to talk about these drugs in our clinics and how we use them. First, I'm going to introduce Pablo. 

Pablo Saenz, PharmD: Hi, my name is Pablo Saenz. I am a pharmacist based in Austin, Texas. I'm a pharmacy manager of one of our pharmacy Texas Oncology clinics. 

Yorio: Next up we have Meagan. 

Meagan Farnie, BSN, RN: Hi, I'm Meagan Farnie, and I'm a nurse here at Texas Oncology in Austin and currently serving as the supervisor over the infusion room. 

Yorio: Great. And then we have Dean. 

Dean Tuel: Dean Tuel. I'm a patient here in Austin, Texas with Dr Yorio and the other people that are on the call. 

Yorio: All right, great. Thanks for joining me everybody. As we think about approved immunotherapy options for our GU cancers like renal cell carcinoma and bladder cancer, there's actually several different drugs that are approved. In fact, 5 total are actually FDA-approved now in different iterations. 

When we look at the different types of immunotherapies, most of these are PD-1 or PD-L1 inhibitors. So, these are checkpoint inhibitors, which are basically designed to try to get your immune system to recognize and attack the cancer cells. The cancer cells have a way of hiding, of course, from the immune system, and these drugs help unlock that. 

There's PD-L1 inhibitors that are approved: avelumab, durvalumab, atezolizumab. There's also PD-1 inhibitors that are approved: pembrolizumab and nivolumab. For our conversation, we're going to mostly focus on our PD-1 inhibitors since they are the drugs that actually have a subcutaneous form as well. 

Pembrolizumab is a PD-1 inhibitor that now has both an IV and a subcutaneous form that's approved. It's approved in renal cell carcinoma and in bladder cancer. Pembrolizumab in renal cell carcinoma is used primarily as an adjuvant treatment for high-risk stage 2 disease, for stage 3 disease, and then for stage 4 disease that's been able to go through surgery. So, that's used as an adjuvant therapy after surgery. 

For our stage 4 patients with renal cell carcinoma, pembrolizumab is approved in combination with several different TKIs with axitinib and with lenvatinib as well as options. So, now there's both an IV and a subcutaneous formulation of pembrolizumab available. 

For nivolumab, nivolumab is also approved in metastatic renal cancer. It's approved in combination with ipilimumab as a frontline therapy, so a dual immunotherapy formulation. It's also approved with the combination of cabozantinib as another option to use. 

In bladder cancer, pembrolizumab is an approved drug to use with another drug called enfortumab vedotin, which is an antibody drug conjugate. We use that in a frontline metastatic setting, and we're also using it in perioperative settings in bladder cancer. Nivolumab also can be used in the perioperative settings in bladder cancer, as well as upfront treatments in metastatic cancer when combined with chemotherapy. 

So, lots of different uses for these drugs for sure. I don't want to belabor all the data and all that stuff too much, because I really think what we want to focus on is this idea of how do we choose these different regimens and maybe thinking about the use of subcutaneous versus IV treatment. 

Just as kind of a background, most of these drugs initially were tested in the IV formulation. But then, they did some studies where they would compare IV pembrolizumab to the subcutaneous form and also IV nivolumab to the subcutaneous form and saw similar efficacy as well as similar pharmacokinetics, so seeing that the drug was staying in patients in the body for a similar amount of time and those type of things. 

Pablo, I'm going to start with you. What have you seen as subcutaneous pembrolizumab, nivolumab has started to enter to the clinic? What have you seen regarding that? I guess what are your first impressions? 

Saenz: Yeah, no, it was obviously very exciting and of great interest for patients that mainly that time factor becomes critical. When you can save any amount of time in the time that you spend in clinic, having something administered sounds great. Naturally, most often the questions that come up are, well, is this going to be just as effective as the IV formulation, or should I stick it out with the IV formulation? 

Thankfully, we do have data that supports that, that supports the interchangeability of it. I think that's the most important factor is driving the education behind for patients and everyone in the clinic that we do have an option that does not lessen the capacity for it to work. 

Yorio: Operationally, Pablo, is it a big change for you guys in the pharmacy as far as the IV formulation versus the subcutaneous formulation? 

Saenz: Yeah. This is an important factor because anytime a new formulation or drug is introduced, there are naturally of course insurance hurdles. I think in the rollout, once everything was sorted and approved, it was a pretty seamless transition. Thankfully, we are seeing these drugs be approved by insurances where appropriate, and it's become operationally at least a seamless transition whenever we want to use that. 

In terms of workflow within the pharmacy, Meagan can also speak to this in some regard, but the process is a lot easier, of course, as a single draw in the pharmacy. It introduces a lot less from a very basic putting-it-together standpoint. Yeah, that's been pretty seamless and helps us save time and resources that we use to actually create these things. 

Yorio: Meagan, what have you seen as these subcutaneous forms have started to enter our clinics and infusion rooms? 

Farnie: Yeah, I would say to Pablo's point, that a big concern that I've heard from patients is just, is it the same? A lot of people will think that because it's a shorter administration time, that it's less effective or it's not as strong as the infusion. There was initially some pushback on that until some education was provided that it's the same efficacy, so that is helpful. 

I think if a patient is only coming in for, let's say, pembro after all of their regimen is complete and they're on maintenance pembro, just a quick injection is much more valuable to them because they get their time back as opposed to, I mean, granted pembro IV is only given over 30 minutes, but the injection, it can be 3 to 5 minutes. 

So, they're getting a lot more of their time back and quality of life is improving for these patients as well. As far as operational or workflow, as Pablo said, it's pretty much the same. We still go through the same process, still look at the same lab values, still have to wait for the drug to be mixed by the pharmacy. All of that really didn't change too much, but the administration time is a big part of the time that the patients would spend here. 

Saenz: Dr Yorio, if I could add just to piggyback off that, I do think it's important to also mention there's data surrounding the drugs themselves, maybe not the interchangeability of the formulation, but showing quality of life. Also, evaluating that, which I think is important to what you both have spoken to. 

Yorio: We all know these drugs carry with it potential toxicities with immune-related toxicities. Are people letting their guard down a little bit because it's a subcutaneous shot that they're only coming in for a few minutes compared to an IV treatment or anything like that where maybe they think it's not going to have the potential to cause as much side effects? Has anybody noticed that? 

Farnie: That's a great question. I personally haven't noticed that in the patients. Like I said, I think they're more concerned about if it's going to work the same. What's the difference between an IV infusion versus a subcutaneous injection? All we have to say is you're getting more time back. It's all the same, and so you're going to experience the same side effects. 

I think my team is really good about educating the patients. We're constantly going over the drugs, even if they've had it a million times. We're still always talking about it, new things come up. I haven't personally noticed that, but I could see where that would be something that some people might think. 

I think it all goes back to the patient's perception of the length of infusion time or administration time with it being less effective, so they might have less side effects. I think a big part of that is education, for sure. 

Saenz: To your point, I think it's a maybe broader conversation for institutions to make sure that they are emphasizing the monitoring remains similar, for the institution itself to not let their guard down on how they are behaving around the administration or treating the patient because to your point, the time difference doesn't necessarily equate to anything else. 

Yorio: Now I'll throw it over to Dean. I mean, he got to experience both ends where he was getting an IV formulation of this and then transitioned into the subcutaneous form. What have been your thoughts about that, Dean, and what differences, concerns, all those things have you noted from your side? 

Tuel: On the front, of course, you are concerned, does it work? Because if it doesn't work, it doesn't really matter. But once you get comfortable and you're able to trust the data that says it's going to work, so once I got past that, I'd say there's probably 3 advantages. 

One, y'all mentioned there's just simply less time there. It's a little bit compounded in the fact that before you even show up, most patients, I suspect, if they're anything like me, you get your game face on before you even show up at the building. You've got to get yourself prepared well when you know that you're just getting a shot as opposed to somebody sticking something in your arm, or I guess some people use a port. It just lessens the game face that you have to get prepared for. 

So, there's less anguish on the front end of even showing up. Then, of course you get the benefit, as you mentioned, about being there less. It roughly saves about 30 minutes or so of the time that I'm there. 

The third thing is that, frankly, it's not as painful. I showed up in the past when I was getting an IV, they have to find a vein in my arm, and that just hurts. In this case, they're grabbing some portion of my belly, hopefully not the fast part, maybe the fast part. I can barely even tell it's there, like it's bone. They sit there for a couple of minutes, squeeze it into my body, and then boom, I'm out the door. It's painless. So, now you're just praying that it actually is effective. 

Sometimes you think about it like when you were a little kid, the medicine that tasted bad when you had a cold is probably the one that worked the best. When you get a little bit worried that, is this going to work since it's far less painful? Maybe it should be painful, maybe it should simulate some pain just so you feel like it's effective. 

So, there's all those benefits that I would say, at least from my experience. As far as I can tell, I don't have any other side effects. Other than going in and getting this done once every 3 weeks, it does not affect my life in any way. 

Yorio: Thanks for that perspective, Dean, for sure. Let's close this chapter out. We're just looking at, again, subcutaneous immunotherapy options available for the GU space, and we'll move on to our next chapter. Dean helped us segue a little bit into that, which is advantages of subcutaneous immunotherapy for patients.