Safety Profiles of Treatment Regimens for Clear Cell RCC


Expert perspectives on how adverse events differ among the available clear cell renal cell carcinoma treatment options.


Robert J. Motzer, MD: One of the most important aspects of treatment for RCC [renal cell carcinoma] in all…patients [with cancer] across the board is the safety profile and managing adverse effects so we can assure that patients are treated with as few adverse effects and manageable adverse effects as possible. I can’t overemphasize how important safety is to our patients. The different programs that we have do have different safety profiles, and these need to be taken into account when deciding on a treatment program for a patient.

In terms of first-line therapy, I generally think either IO [immuno-oncology]-IO with ipilimumab-nivolumab or IO-TKI [tyrosine kinase inhibitor] with one of those combinations, and the safety profile is quite different. For ipilimumab-nivolumab, the safety profile is all about immune-related toxicity. And in general, I have found that the immune-related toxicity occurs most frequently during the induction period when ipilimumab is given with nivolumab. And I think during that period, patients need to be monitored very closely. We need to be familiar with what those immune-related adverse effects are and how to manage them. Common ones include hypothyroidism or an effect on the thyroid. I frequently monitor that. I usually monitor the thyroid function test every cycle with ipilimumab-nivolumab. Also rash, hepatitis, and certainly diarrhea and colitis are adverse effects that are quite common. And then after that, there are more infrequent but very important immune-related adverse effects that need to be watched out for and detected very early. And because they are so different, one needs to be really careful to watch any change in the patient and to perhaps see if that could be related to an immune effect. For example, Sjögren syndrome is one that I see. We’ve also seen neuropathy and type 1 diabetes. It’s very important for the medical group managing the patient to be familiar with that and be on close watch.

The TKI-IO combinations have a different spectrum of toxicity. Certainly, immune-related adverse effects occur, but they seem to occur less frequently than [with] ipilimumab-nivolumab. And many of the adverse effects associated with the tyrosine kinase inhibitor and IO combinations are driven by the tyrosine kinase inhibitor—lenvatinib, cabozantinib, axitinib—and they include hypertension, diarrhea, skin toxicity, rashes, and so forth. These also need to be managed over time. One of the benefits of those particular programs is that they are more predictable and many physicians have had more experience in terms of recognizing and managing those toxicities, since the tyrosine kinase inhibitors have been in use for…almost 20 years.

On the other hand, the disadvantage of the tyrosine kinase inhibitor and IO combinations is that the toxicities are cumulative over time. And so again, that could impact on quality of life and needs to be managed closely. It’s managed often with dose reductions. We might also offer patients drug holidays where they may stop the tyrosine kinase inhibitor and some of the chronic toxicities like diarrhea and so forth are ameliorated, and other supportive care measures. The adverse events are quite diverse between the two. And even with regard to the 3 different TKI-IO combinations, they reflect that of the TKI. And while they’re all of the same class, the different tyrosine kinase inhibitors demonstrate a different toxicity profile. For example, lenvatinib and axitinib seem to have more hypertension, whereas with cabozantinib, maybe less hypertension but more skin toxicity. The treating physician needs to be aware of those differences and be particularly vigilant and also may make a choice of one regimen or another based on the patient’s individual needs and their comorbidities.

Transcript is AI-generated and edited for clarity and readability.

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