It Takes a Village

I consider this a great time to be an oncologist. When I started my training, we were limited in what treatments we had to offer people with cancer—we only had chemotherapy, and oftentimes, it wasn’t very effective. I remember being on the inpatient service and seeing so many people at the end of their lives, dying from melanoma or lung cancer, or else, dying from the toxicities of treatments that did little to help their disease but that robbed them of any quality time they had left. Today we have options: targeted treatment, immunotherapy, and more precise strategies have changed the way we practice. With these options, though, has come a whole new expectation on how to manage toxicities.

For me, it started with the use of bevacizumab in ovarian cancer. For patients with recurrent disease, it was indeed a lifeline, and even today, I think it is one of our most powerful agents in that disease. However, the side-effect profile of bevacizumab differed from chemotherapy. I had trained to manage nausea, vomiting, constipation, diarrhea, neuropathy—“typical” chemotherapy adverse events. Bevacizumab caused hypertension, and while I was boarded in internal medicine (and still am), it was one of those “other” medical problems I usually referred back to primary care: a “chronic condition” that fell outside my purview as an oncologist. This was different. The hypertension was idiosyncratic and could be severe. I found myself treating it, often prescribing one, two, and sometimes, three agents to achieve adequate blood pressure control. I learned to treat hypertension as a treatment-related side effect, and I learned how to de-escalate antihypertensive medication after bevacizumab had been discontinued,  whether due to disease progression or toxicity. While I took on that job, I admit that I was not comfortable doing it. I spent many hours reviewing blood pressure logs and checking in with patients outside of their scheduled appointments. As the use of bevacizumab increased in my practice, however, I found it untenable to manage hypertension for so many patients by myself. Ultimately I learned to engage primary care physicians early on by letting them know when their patients were starting bevacizumab and proactively soliciting their help in the management of any resulting hypertension.

If that was a learning curve, immunotherapy has taken managing toxicity to an entirely new level. Standard treatments such as the CTLA-4 inhibitors and immune checkpoint inhibitors can wreak havoc on almost any organ system, knocking out thyroid function, resulting in liver dysfunction, and rarely, inducing life-threating cardiac abnormalities, just to name a few. I find myself reading up on management of toxicities as they arise, following best practice to the best of my ability. The American Society of Clinical Oncology (ASCO) along with the National Comprehensive Cancer Network (NCCN) has even published clinical practice guidelines on managing immune-related adverse events (irAE)—a document that spans 54 pages [1].

It is incredibly important to have such guidelines, and although I am grateful to see it published, I still have that feeling of discomfort reminiscent of when I first started using bevacizumab. Indeed, it’s even more intense. It’s not that I don’t think I can manage the side effects of these new treatments—I am sure I can. It is more the feeling of whether I should be managing them, let alone doing so without help. To be clear, this is the not the viewpoint of any immunotherapy specialist within our field, nor is it the guidance offered in the ASCO guidelines. If I am honest, the sense that this is something I need to do stems from a deep-rooted belief of what it is to be an oncologist. To me, oncologists must understand the drugs we give, including their toxicities, and how to manage them effectively.

In this brave new world, though, my experience with bevacizumab is helping to instruct my management of these toxicities—through proactive engagement with other medical specialists. See, as oncology evolves, I believe we can no longer practice as we have done in the past. If there’s anything immune-oncology teaches us, it is to respect the adverse events these therapies can cause and to embrace the role other specialists must play in the safe treatment of our patients.

I’ve come to the conclusion that we must create our own multidisciplinary teams to manage these patients, teams that include cardiologists, endocrinologists, pulmonologists, gastroenterologists and hepatologists, dermatologists, and nephrologists. At some comprehensive cancer centers, this approach has led to the creation of a specialized case management conference (or an irAE Tumor Board, such as the one at the Cleveland Clinic, as reported in “Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash,” by Pradnya D. Patil et al.), while in others, it has led to specialized inpatient teams. The need for such multidisciplinary care, however, should not be limited to NCI-designated centers. Hillary Clinton famously stated that “it takes a village to raise one child.” I believe the same can be said about the safe administration of immunotherapy to our patients—perhaps not a village, but most certainly, a team.

References:

1. Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology 36, no. 17 (June 10 2018) 1714-1768.