The Oncology Nursing Society (ONS) recently collaborated with the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) to create a guideline for best-practices management of immune-related adverse events (irAEs) in patients treated with checkpoint inhibitors—anti–programmed death 1 (PD-1) antibodies, and anti–programmed death ligand 1 (PD-L1) antibodies. These immunotherapies are now approved for a range of different solid tumors and hematologic malignancies. These drugs have side effects that are distinct from those that can accompany treatment with oral targeted agents and those that can accompany chemotherapy. This guideline is published in the Journal of Clinical Oncology. Today we are speaking to one of the authors of this guideline, Kelly Brassil, PhD, RN. Dr. Brassil is the director of nursing programs at the University of Texas MD Anderson Cancer Center, in Houston.
—Interviewed by Anna Azvolinsky
Cancer Network: First, what was the process by which you and your coauthors developed this guideline to mitigate adverse events related to cancer checkpoint inhibitor antibodies? What is the guideline based on?
Kelly Brassil: Thank you for having me. The ASCO/NCCN guidelines represent the work of an inter-professional panel of physicians, nurses, and patient advocates who gathered to provide their expert feedback on their observations of toxicities and their management, specifically related to checkpoint inhibitors. The guidelines were based on a systematic review of the literature related to the occurrence and management of immunotoxicities. Given that this is really an evolving field, many of the recommendations were ultimately based on expert opinions that were achieved through panel consensus. While there is robust literature from investigative trials on these agents, there are fewer articles that speak to evidence-based management of their toxicities.
So, the panel members were broken up into groups that focused on specific system-based toxicities. They made recommendations based on evidence in the literature as well as their expert opinions and experiences, and then they made recommendations on toxicity management by system. The guidelines were then brought together into a merged document for review by the entire panel of experts. And there were several iterations that went back and forth between the authors and editors, after which they were opened for public feedback. So this allowed for individuals outside of the panel, who had clinical practice expertise and other knowledge, to provide feedback, recommendations, and queries on the content that was provided.
This information was then given to the panel for additional responses to be made before final revisions were put into place by the lead author. And that was the process, which was very organic [and] based as much on existing evidence from research, and science, and the literature, and the clinical experience of the individuals who provide this type of care every day.
Cancer Network: Did you see something specific in your own care of cancer patients who receive checkpoint inhibitors that warranted such a guideline?
Kelly Brassil: In my current role as a director of nursing research and innovation, I have been involved in clinical trials with checkpoint inhibitors and as part of the IRB review and in the support of nurses providing clinical care to these patients. What is so exciting is that the immunotherapeutic approaches are continually emerging in the context of both research studies and clinical care.
When we think about the checkpoint inhibitors, the ones that come to mind most readily are nivolumab and pembrolizumab, and they are increasingly becoming standard of care for an expanding diversity of indications. As research continues to evaluate and establish new indications, including disease types to which these agents can be applied, as well as the combination of agents with other cancer drugs, we really have a need to identify the toxicities unique to these agents alone or in combination. And these toxicities are being observed both in clinical trials and in standard of care management of patients.
To understand the importance of the guidelines, it is fundamental to understand how immunotherapy works, and how it is unique from chemotherapy or radiation or the traditional targeted therapies we use in cancer care. To put it simply, whereas chemotherapy and radiation are used to kill malignant cells both specifically and nonspecifically—and can often cause toxicities to healthy tissues in the surrounding areas, immunotherapeutic agents target specific markers within the immune system to either initiate or suppress an immune response, ideally resulting in regression of malignant cells.