Role of Combination Therapy in RCC Management


Dr Thomas E. Hutson comments on the rationale for using combination immune therapy, as well as a combination of immune therapy and an oral VEGF inhibitor for initial treatment of RCC.

Thomas E. Hutson, DO, PharmD: Speaking about combination therapy, the next therapy to consider using as initial therapy is a combination of one immune therapy with an oral therapy, a VEGF [vascular endothelial growth factor] inhibitor. The rationale is that we know that the VEGF inhibitors play an important role in controlling and treating the cancer by blocking blood vessels, and we know that’s such an important target for treatment in renal cell cancer. The hope is that we will get all the benefits of using the VEGF inhibitor. With the addition of the checkpoint inhibitor, the immunotherapy, being able to turn on the immune system, that it would be almost a one-two punch where you’re able to shut off blood supply, help work on killing the cancer and turn on the immune system so the immune system recognizes the cancer and fights.

You have now 2 modes of attack. Early studies of doing this have shown us a couple of important things. One, it’s rational in that the combination produces a better response than either agent alone. Also, we’ve learned that not all the oral VEGF inhibitors are combinable to the immunotherapy. In fact, there are only a couple. What’s on the market that you may hear your doctor mention, or you may come across in your readings is an oral therapy called axitinib. There’s also an oral therapy called cabozantinib. What has been recently presented was an oral therapy, lenvatinib. Each of these oral therapies has been shown to be combinable with checkpoint inhibitors

That combination can produce significant degrees of benefit. With the combinations, we see response rates, tumor shrinkage rates, of 70—the ability to at least stabilize the cancer in 90% of patients. Like we saw with the two-immune-drugs combination, the ipilimumab-nivolumab combination, we’re also seeing complete responses. You may say, “If you’re doing that, then we might as well just go with the immunotherapy and the pill.” Well, it’s not as clear. The two immune therapies, the ipilimumab-nivolumab, have been on the market now for almost five years, and we have a long-term follow-up with them. We know that the responses that are occurring with the ipilimumab-nivolumab are durable for years.

Unfortunately, for the immune therapies and the pill combinations, we don’t have as long of data. It’s unclear whether we should be thinking of them as interchangeable. Right now, they’re both options, and you’ll find your doctor choosing one or the other approach. For various reasons, that’s an area that we’re investigating to try to determine which strategy is the best for any given patient. As a result, as you’re having your conversation with your doctor and talking about the initial therapy, you may want to ask him, “Why are you choosing this particular therapy over this other one?” I’ve already told you that there’s no definitive right or wrong answer. They’re both acceptable treatments. We tend to use and individualize them for our own purposes in individual patients, and it’s a good question to ask.

To complete our talk about first-line therapy for metastatic kidney cancer, we have to mention that not all patients who we see would be a candidate for immunotherapy. All we’ve talked about were immunotherapy, either combinations or with a pill, so there are reasons why we wouldn’t want to give an immunotherapy. For instance, patients who have ongoing, active autoimmune disease. These would be things like rheumatoid arthritis, lupus and psoriasis. They could be patients who’ve had organ transplants. Patients with severe Crohn’s disease or ulcerative colitis. A variety of these autoimmune diseases would use one of these immunotherapies, which turn on the immune system, making them wrong, dangerous and not recommended. In that setting, what we’d consider using, which is now recommended in that setting, is an oral therapy. The oral therapy that’s given the highest level of recommendation is cabozantinib. Thus, cabozantinib becomes that third possible choice.

This transcript has been edited for clarity.

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