Evidence-Based Guidelines Needed for Immunotherapy-Related Adverse Events

Matthew Burke, MBA, RN, MSN, APRN-BC

As more immunotherapies move from the bench to the bedside, oncology nurses need to develop a thorough understanding of how these treatments work, as well as how their adverse event profiles differ from those typically seen with traditional cytotoxic regimens, including immune-mediated effects on vital organ systems. Studies combining multiple immune-modulators have reported grade ≥3 immune-related adverse events (IRAEs) in up to 50% of patients,¹ highlighting the need for evidence-based guidelines to support the clinician in helping patients to safely manage these events.

This is the goal of research underway by Matthew Burke, MBA, RN, MSN, APRN-BC, Nurse Practitioner, Melanoma and Renal Cell Carcinoma Team, Smilow Cancer Hospital at Yale New Haven in Connecticut. He and colleagues are currently analyzing data from several ongoing immunotherapy phase I and II clinical trials with the goal of developing case-based approaches for use with patients experiencing serious IRAEs.

Oncology Nursing News sat down with Burke at the Oncology Nursing Society’s Connections conference held November 7-10, 2013 in Dallas, Texas, to learn more about this research.

Oncology Nursing News: Why are immunotherapies garnering so much attention right now?

Burke: In melanoma, for example, we have changed the paradigm for treating cancer in our clinic. We were used to drugs where we had patients responding 5% to 10% of the time. Of 10 patients in our clinic, very few of them would go on to achieve a durable response and survive and live past their 6-month life expectancy.

Now we have drugs where large numbers of patients are getting 30%, 40%, 50% response rates—durable, meaningful responses from these drugs. That changes our practice. It changes what you tell your patients; it changes how we practice oncology.

What’s also interesting is that it’s not just one disease. It’s not just melanoma or renal cell carcinoma. We’re seeing activity with these agents across the board, and there are studies going on right now using these drugs in all kinds of different cancers.

This is a paradigm shift in how we treat cancer. It’s not just about a new drug or even a new class of drugs. That’s why this topic received a lot of attention at ASCO this year and why we’re going to see it really become the topic that we’re talking about across the board—whether we’re talking about new drug development, or managing the side effects of these drugs appropriately with evidence, or even how to interpret the responses, which is a whole new area in itself: how we interpret patients’ responses to these drugs differently from chemotherapy.

With chemotherapy, when we looked at a tumor and saw regression, it must be working. With these drugs, patients can have pseudo-progression or a partial response, and it’s all meaningful. And, these patients are living longer, and that in itself is meaningful, because we now talk about survival as opposed to just response rate.

Generally speaking, how prevalent are adverse events associated with immunotherapies?

What I tell my patients is, approximately onethird (30%) will develop clinically significant or, possibly, moderate-to-severe side effects. This generally applies across our three major areas of concern: dermatitis, enterocolitis, and endocrinopathy. When you think about immunotherapy, you can add an “itis” after any side effect, but these are the “big 3” in our clinic.

What are some of the ways in which the side effects of immunotherapies differ from those of traditional chemotherapies?

These are immune-driven side effects, unlike traditional chemotherapy, where we give a patient a drug, they get sick for a few weeks, then get better, and most of those side effects are limited to the time the drug is in their body. As the drug gets metabolized and excreted, those side effects tend to wear off. There are some exceptions, as patients can get long-lasting neuropathies, for example, but these are direct effects of those drugs. Immunotherapy is different, because these agents cause modifications in the checkpoints of the immune system that we suspect may be permanent or last a very long time. We don’t actually know.

In addition, the severity of these events can be much worse. We see patients who have really life-threatening endocrinopathies or rashes, which we do see in very tiny numbers with other drugs, but not to the extent that we do with these drugs. They’re clearly different, and because of the immune system driving these, the severity can be much, much worse.

The challenge, of course, is that it’s hard to predict who is going to be developing these effects and who is not, and that is certainly an area where we would like to learn more.

Tell us about the research you are conducting to develop evidence-based guidelines for oncology nurses.

We don’t have a lot of evidence at this point to support how to manage these events. When you travel around the country and talk to different people—even those who are experts in immunotherapy— they all have a little bit of a different way of managing some of these side effects. It’s our job as oncology nurse practitioners and clinicians to help develop some of the evidence that will formulate the guidelines on how to manage these.

Most of the guidelines for how to manage these toxicities have come from the guidance that we are given out of clinical trials. When these drugs are developed, you have patients on protocols, and the protocol will say, for example, “if they develop this side effect, you do this.” Those guidelines have become our practices in the clinic. That doesn’t mean they’re evidence-based.

We don’t have great guidelines right now. There is a real challenge for us to look at these side effects and to attempt to quantify and qualify them much better, and then to develop really good evidence-based guidelines for how to manage them.

Reference

• Burke M, Hoffner B, Rubin K. Management of selected toxicities associated with the use of immune checkpoint modulators. Oncol Nurs Forum. 2013;40(6):E419.