Subcutaneous vs IV Nivolumab: A New Frontier in RCC Treatment Delivery

In the fourth segment of our roundtable series on advanced renal cell carcinoma, Michael Atkins, MD, and a panel consisting of Laurence Albiges, MD, PhD; Chandler Park, MD; Mike Lattanzi, MD; and Alan Tan, MD, evaluate the potential benefits of subcutaneous nivolumab versus IV nivolumab for patients with metastatic kidney cancer. They explore the advantages in terms of patient convenience, infusion center capacity, and potential cost considerations. The panel also examines how the sub-Q formulation might affect clinical practice and patient management.

Watch the fifth part of this series: Overcoming Access and Treatment Hurdles in Community and Academic RCC Care

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Dr. Atkins:
Okay. We’re going to move on to… There was a study presented at GU ASCO last year, and I think an update at ASCO last year, looking at subcutaneous nivolumab compared to IV nivolumab in patients second line after VEGF-TKI with metastatic kidney cancer. And Laurence, do you want to describe the results of that study? 

Dr. Albiges:
Yeah, sure. So I think as a concept from a patient perspective as well as from a healthcare provider perspective, we need to think about how we can reduce the burden on the patient. And subcutaneous has been for systemic therapy in oncology has been developed first in heme oncology then in breast cancer. And so there are already agents available that are administered subcutaneously routinely. With regard to immune checkpoint inhibitor, that started a few years ago with atezolizumab in lung. But for GU oncology, we didn’t yet have any data. And so what the study demonstrated was to look at the administration of subcutaneous nivolumab compared to the IV. And because it’s a change of modality, a change of root, you have to show that it is the same pharmacokinetic. So the co-primary endpoint are actually PK endpoint. And it was basically I would summarize as the average exposure up to the drug. And so the co-primary endpoint were non-inferiority phase three design were met. But the study was also powered to go for clinical relevant endpoint to us, which is response rate, and there’s also PFS and of course ultimately overall survival. 

And so to put a long story short, the study demonstrated not only the non-inferiority of the sub-Q approach, but it is interesting to stress that the level of exposure was actually a bit higher in the sub-Q arm. The response rate was actually a bit higher in the sub-Q arm, and the PFS was a bit longer. So the study was published in analysis of oncology. It’s very likely that it’s going to lead to a filing, and I hope in the future an approval because I think that will really change for our patient, their daily management. And so it’s one sub-Q administration every four weeks. Of course it’s hospital administration, but that’s a five minute sub-Q versus 30 to 60 minutes IV. So I think it’s very relevant and I believe that it’s not for the induction phase where you want to carefully monitor your patient with ipilimumab. But as soon as you’re in the maintenance phase, that Chandler was referring to, that could be extremely convenient for the patient. And with regard to toxicity, there was no increased toxicity. There was a higher level of ADA in the sub-Q arm as anticipated and as previously demonstrated with other agents, but that was not as associated with more side effect or more immune related toxicity. 

Dr. Atkins:
Great summary. Alan, let’s assume that sub-Q nivolumab is going to be approved for kidney cancer, do you anticipate using it and in what patients? 

Dr. Tan:
I think it’s a discussion to be had with patients. In my personal opinion, it doesn’t move the needle too much because I personally think 30-minute infusion is quite good for patients when you compare it to say, Jim Satterbean’s cisplatin, where they are there the whole day. So I guess from a convenience standpoint, I would want to see more done in the field where you can maybe do infusions remotely. I think there’s more telemedicine being done these days. If a patient can get blood work at a local lab and then have a telemedicine visit and then actually assess scans and results remotely, I think that’s probably where it might have a bigger role. As far as the efficacy, I think it’s probably comparable, even though Laurence mentioned there was actually surprisingly an increase overall response rate. 

Dr. Atkins:
And if it was administered outside the hospital, would that be administered by a healthcare professional or do you foresee patients administering it? 

Dr. Tan:
Yeah, I can’t see patients doing with an oncolytic. I know we allow patients to get their own self-injectable new LASTA. But as far as an oncolytic, I’m not so sure we’re ready for that. I think it needs to be with a trained APP perhaps that comes to your house. 

Dr. Atkins:
Okay. How about in community practice? 

Dr. Lattanzi:
Yes. I think this is one of the areas where practicing in independent practices probably quite similar to academia. And I think we all face challenges around the time it requires for some of these longer infusions and just the sheer capacity of our infusion centers and not being able to meet the needs of the patients. I think sub-Q formulations are definitely an important part of the solution to that problem. I can tell you in my own practice, we had a gynoch join our office a few months ago, and as a result, there are a lot of really long infusions for these GYNs. And as a result, many of the other doctors who may practice more GU or melanoma or whatever are having more challenges scheduling our patients for their infusions. A sub-Q formulation would be really helpful to ease some of the challenges on infusion capacity. In terms of this hospital at home concept, I actually don’t think it’s terribly burdensome for the patient to come to the office. Most of our patients live nearby our offices and our practice is designed in such a way that we’re physically nearby the patients. And I think coming in, even if it’s just for a five-minute injection, is also an opportunity to, one, be assessed by your doctor, review the labs, and have a conversation about the trajectory of your care. 

Dr. Atkins:
And so you would envision in your practice that patients would get the injection at their visit? 

Dr. Lattanzi:
I think so. I think I imagine using it similarly to how we utilize maintenance nivolumab, post Ipi-Nivo now on the same schedule, but just with a lower demands on the infusion center. 

Dr. Atkins:
And Chandler, how about you? And also do you envision using it for Cabo-Nivo combination? 

Dr. Park:
Yeah, I am very excited about this data. And just to highlight some of the different stakeholders in this and go to your question, I feel like if you look at it from the patient’s perspective, it’s a huge win. I agree with Alan five minutes versus 30 minutes, but it’s the perception time. And also with the facilities, they get patients in and out much faster, five minutes versus 30. But then you have to also think about the stakeholders in terms of the payers. We’ve had this in Kentucky and I’ve had colleagues in Michigan where the payers actually dictate some of these IV treatments to be given at another facility and maybe an APP or a pharmacist is there. And so we’re actually seeing that right now in Kentucky and Michigan. So the payers play a huge role in this. In terms of convenience, I think it’s a win for the oncologists and the patients. 

I’m concerned about the toxicity follow up because even though this is still easy, the side effects, we have to monitor the endocrinopathies. And then we have to also think about the combination where we have the Cabo-Nivo. The Cabo piece, it does have side effects that build over time. And so I’m going to try my best, once I have the studies come out that shows “similarities” in terms of the CheckMate 9 ER and see what the data shows. But even if it’s approved, I still want to see the patients at least once every 28 days. And when they start the treatment, I want to follow their CMP and the LFT, so. 

Dr. Atkins:
So I think everybody still wants to get blood tests and see the patient, maybe not necessarily directly in your office, but feel that there’s some advantages in either efficiency at your office or convenience for the patient in having the option for sub-Q. And I think that’s great. I hesitate to ask this question, but do you think that cost of treatment will factor into this decision-making in both what you do and what insurance companies do? 

Dr. Park:
Yeah, I think we win on a pragmatic society. All of us are on the front line, we see patients and we try to do what’s best for our patients. But if we’re in a hospital-based facility or university-based facility, that is definitely going to be part of the equation. So sometimes even with pathways, this it might come up. So I do think that’s going to be a role. 

Dr. Atkins:
How about anyone else? 

Dr. Lattanzi:
So the payers provide all kinds of constraints on the drugs that we’re able to administer. They leverage both the practices and the hospitals in terms of contracting for the drugs. And also to some extent the patient who we’ll prescribe blood thinner, we’ll prescribe an antigen receptor pathway inhibitor or we’ll prescribe whatever and find out that the patient has a large co-pay. So the realities of our system are the cost will undoubtedly be a factor for most patients in this case. Fortunately from a PD-1, so from a clinical standpoint, I would expect the same efficacy. 

Dr. Atkins:
And Laurence, how about in Europe, do you think? 

Dr. Albiges:
I’m going to decline this question because we’re so different in how we are funding and each country in Europe has a different reimbursement mechanism. So I think it doesn’t really apply to the US strategy. 

Dr. Atkins:
Okay. Alan, you want to- 

Dr. Tan:
I’m a consultant to the patient and I try to do what’s best for the patient. If a payer tells me that I have to choose a select route, then I deal with it maybe after a first appeal, but I try not to get involved with finances.