By Cathy Clark, APR - June 22, 2020
Fatigue and insomnia are the most common and severe patient-reported toxicities of immune checkpoint inhibitors (ICIs) for head and neck cancer, but cognitive behavioral intervention may help, Moffitt Cancer Center researchers reported.
“While much is known about clinician-rated adverse clinical events of immunotherapies from clinical trials, less is known about patient-reported toxicities,” said behavioral oncologist Dr. Heather Jim. She is one of the authors of an abstract that described patient-reported toxicities in head and neck cancer patients treated with immunotherapy. Jim and colleagues submitted the abstract which was presented at the 2020 American Association for Cancer Research virtual annual meeting II held June 22-24.
“In clinical trials, fatigue is one of the most common clinician-rated toxicities, but the rates in our study of patient-reported fatigue were much higher,” said Jim.
Immunotherapies such as nivolumab and pembrolizumab are FDA-approved agents used to treat various head and neck cancers. “Advantages of immunotherapy in treating head and neck cancer include durable clinical benefits in patients who respond to the treatment compared to palliative chemotherapies,” said medical oncologist Dr. Christine Chung, one of the abstract authors.
Although immunotherapy for head and neck cancer is significantly less toxic compared to chemotherapy or radiation, it is not entirely toxicity-free. “Treating physicians may be underestimating the severity and impact of toxicities on quality of life of the patients because they are focused on managing incurable cancer,” said Chung. “It is important to adequately capture the whole patient experience.”
Patients with head and neck cancer were recruited as part of a larger study on quality of life on immunotherapy. Clinician-rated adverse events and patient-reported toxicities are complimentary to one another. They provide a sense of what's going on medically with the patient from the clinician perspective, as well as the treatment experience from the patient perspective.
“The gold standard for assessing things like pain or fatigue is the patient report, because it's a subjective experience. There's no way you can measure fatigue like you can measure blood pressure,” said Jim. “Clinician-rated adverse events are reporting on toxicities through the filter of the clinicians' medical education and experience, while patients are reporting on their own symptomatic toxicities in a firsthand, unfiltered way. If a symptom like pain or fatigue or sleeping disruption is distressing to the patient, then that's something that probably warrants clinical attention.”
The findings draw attention to some of the side effects that patients experience during immunotherapy, and it can help in educating future patients about what to expect during treatment. “This can help patients who are experiencing these side effects know that they're not alone, that these are pretty common and there's not something going wrong,” said Jim.
Next steps include more cognitive behavioral studies to learn better interventions for patients experiencing treatment-related fatigue. “We're starting to get an evidence base that fatigue is a common and one of the most severe side effects of immune checkpoint inhibitors,” said Jim. “We know that some patients are on these treatments long-term, and we can start to do studies to see whether cognitive behavioral intervention is effective for fatigue related to treatment with immunotherapy.”
Jim described a separate cognitive behavioral intervention study related to fatigue in which the researchers found that typical things one instinctively does for fatigue, such as taking a nap or cutting back on activities, do not help for cancer-related fatigue. “In cancer patients, that actually contributes to the fatigue by causing patients to become deconditioned due to lack of activity. If they're napping a lot during the day, their sleep schedule gets disrupted, making matters worse and causing some patients to feel helpless about their fatigue,” said Jim. To address the situation, Jim and colleagues worked with the patients to regulate their activity, slowly increasing physical activity and helping patients sleep on a more regular schedule. “Then their thinking about the fatigue started to change and they began to feel that they had more control over the fatigue.”
There is an increased focus from the FDA, academia and industry on measuring through clinical trials patient-reported outcomes like symptomatology, disease side effects and quality of life in patients on new treatments. Jim and Chung hope to see more studies with broader demographics in order to gather better real world evidence from patients. “Generally speaking, patients on clinical trials tend to be younger and healthier on average and less racially and ethnically diverse than those treated in the community,” said Jim. “It is going to take large studies in cancer centers and community clinics around the country to really adequately capture the demographics of the patient population.”
Additionally, they want to see better ways to measure patient-reported outcomes beyond the end of a particular trial. “Typically, once the clinical trial ends, so does the measurement of patient-reported outcomes.” Future goals include learning more about patient-reported long-term or late effects of some of the relatively new immunotherapy agents which might be administered over a long period of time.