Video
Role of Combination Immunotherapy in Metastatic Renal Cell Carcinoma
Author(s):
Key opinion leaders in the field of renal cell carcinoma management discuss the advent of combination immunotherapy in patients with metastatic disease.
Transcript:
Hans Hammers, MD, PhD: This patient was what we call intermediate risk. Obviously, they have official criteria. So when a medical oncologist or urologist sees patients with metastases for the first time, we try to put them into a bracket. So this is a patient who required treatment within a year. Some patients may have additional lab abnormalities, in particular, let’s say anemia, for example. Essentially, inflammatory markers of chronic disease, if you will, with anemia. Some classic risk factors such as elevated neutrophil count, elevated platelet count, or hypercalcemia. We look at decreased performance status. So this was a solid intermediate-risk patient. If you have more than 2 of those risk factors, you have poor-risk patients, etc. This is how we go about those patients. A special group are good-risk patients, those are patients who were seen by the nephrologist, treated with surgery, with the intent to cure obviously, and then recur oftentimes years later. And those might be from some special cases actually. So he was treated with nivolumab [Opdivo]/ipilimumab [Yervoy], and just to remind our listeners, this is the first doublet of immunotherapy that was [FDA-]approved later on in 2018. The trial CheckMate 214 pit nivolumab/ipilimumab against sunitinib [Sutent]. Actually, roughly almost 1000 patients, 500 patients in each arm. The curious design was that the primary cohort with the regulatory end points of progression-free survival over a survival response rate was really made up of intermediate- and poor-risk patients. Roughly 20% of patients though, were good-risk patients, but they were not part of the regulatory cohort. When this regimen got approved, it got approved for intermediate- and poor-risk only. Although we do use it for some good-risk patients, and the NCCN [National Comprehensive Cancer Network] guidelines reflect that because some of the patients can also have some very durable responses. The other thing that’s nice to know about this oldest regimen in our armamentarium is that we now have some very interesting, and I think worthy and quite frankly to beat, if you will, long-term end points, 5-year overall survival. That is actually quite favorable with around almost 40% of patients living 5 years. The median overall survival is around 46 months for the intermediate- to poor-risk group, and for the intent-to-treat group, meaning including good-risk patients, almost 56 month. It’s really quite unheard of. Roughly one-third of patients never progresses, so at the 5-year mark, and responses can be very durable. The median duration of response had not been reached at the 5-year mark. So this is a very interesting landmark if you will, and how much immunotherapy has changed the way we treat patients. To my medical oncology colleagues, obviously, this patient actually had autoimmune side effects, so those are the classic side effects if you observe. Nephritis is actually not the most common one, but certainly one that we see in those patients often treated with steroids. Sometimes we need to add additional immune suppressive agents. But clearly, one of the reasons why we may have to stop immunotherapy, and as demonstrated in this case, despite heavy immune suppression, the end of tumor benefit can continue for a long time with the patient, who many of us would now think of is potentially even cured from his metastatic renal cell carcinoma. The other thing I would say that’s important to know or to remember with this regimen is that the quality of life is actually unique in terms of when compared to tyrosine kinase inhibitors [TKI]. We do have some quality-of-life data in comparison to sunitinib. And so we have, for example, another set of 5-year follow-up data in that regard. In general terms, when you start a TKI, your quality of life deteriorates quite rapidly. In patients treated with this particular regimen, it actually tends to improve. And also the time to definitive deterioration, if you will, with more side effects that also has to do essentially with disease progression, is clearly much longer for patients treated with this regimen. And roughly 75% of patients essentially were more likely to be less bothered by side effects than if you had a TKI on board, such as sunitinib. So yes, we do sometimes see these scary side effects with inflammation of the colon, inflammation of the kidney like in this case, inflammation of other vital organs, but those tend to get much better after initiating immune suppressive therapy. So that’s just something to remember, that overall, while some of the side effects can be scary and require prominent intervention, that the quality of life typically is unmatched when compared to a TKI.
Transcript edited for clarity.
