Sriram Yennu, MD, on Cancer-Related Fatigue: Is Open-Labeled Placebo an Effective Treatment?
2022 ASCO Annual Meeting
Sriram Yennu, MD, of The University of Texas MD Anderson Cancer Center, discusses the placebo response in patients with advanced cancer and cancer-related fatigue. His latest findings show that open-labeled placebo was efficacious in reducing cancer-related fatigue and improving quality of life in fatigued patients with advanced cancer at the end of 1 week. The improvement in fatigue was maintained for 4 weeks (Abstract 12006).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Cancer related fatigue is a significant symptom among patients with advanced cancer. Usually the fatigue has significant impact on the patient's quality of life, their ability to do their social activities, and their ability also to get cancer treatment. And unfortunately, there are very limited treatments for the treatment of cancer related fatigue. Right now, physical activity is one best evidence based treatment. Unfortunately, the adherence in advanced cancer is limited, and also it is having a limited impact on all the causative factors of cancer related fatigue. There are several pharmacological treatments started investigated for the treatment of cancer related fatigue, but unfortunately most of the studies were mixed, and there is no FDA approval for the treatment or pharmacological treatment of cancer related fatigue. One of the reasons being is that a single agent doesn't really target all the causative factors. The other reason is that a lot of times when the clinical trials for pharmacological agents are done, they use placebo. When placebo is used, usually there is a good response for not only the pharmacological agent, but also for the placebo. Hence, most of the studies are negative. That's the reason we have conducted a randomized controlled trial using the placebo. The placebo was given in a non-hidden format, that is open label format, that the patient knows that the patient is receiving the placebo. We used a wait list control. That is the patient who is on the wait list control will wait for another week before they get the open label placebo. When we compared these two at the end of eight days, basically the patient has significant improvement of fatigue in the open label. When we asked the patients in the wait list arm to also get the open label placebo after day eight, both the open label placebo and the wait list arm received the open label placebo until one month. At the end of the one month still, there was a significant improvement of fatigue in both these arms after receiving the open label placebo. When we looked at other outcomes, in addition to fatigue, like the fatigue cluster, which is the combination of fatigue, depression, and pain, there's also significant improvement of the fatigue cluster. We also looked at quality of life, both the if fatigue disrupted quality of life, and the general quality of life. There was improvement of fatigue disrupted quality of life, but there was no significant difference compared to the wait list arm compared to in the open label placebo arm. The generalized quality of life was not significantly different in both the arms. Actually, it was better in the wait list arm. The main reason for this difference is that the message was mainly focused when we are trying to give the study in regards to the fatigue rather than other quality of life measures. Hence, there was an improvement in fatigue compared to other quality of life measures. The significance of this study is that the open label placebo, and the format, actually is feasible in advanced cancer patients, and that it significantly improved fatigue. The other important thing is that the improvement of the open-level placebo is as much, or more better, than other pharmacological agents used for fatigue, like the Methylphenidate and the Erythropoietin that was used previously. The other important thing is that the open label placebo had message dependent improvement. That is the improvement of fatigue was mainly focused on fatigue rather than other quality of measures. That has implications for the future thing. What is the implication for general practice? You can use open-level placebo in general practice, as long as you are able to start the open-level placebo and work up on the other causative factors of fatigue. The other important thing is in the clinical trials, you need to account for the placebo effect, while at understanding the effects of various pharmacological agents for fatigue. Lastly, the most important thing is that you can use placebo as one of the interventions to add on to the pharmacological agents to treat fatigue. It can be an adjuvant or add-on treatment in addition to the pharmacological treatment. These three are most important implications of this study.
Pamela L. Kunz, MD, of the Yale University School of Medicine, discusses new findings from the ECOG-ACRIN E2211 trial, which showed the longest progression-free survival and highest response rates with temozolomide plus capecitabine reported to date for patients with pancreatic neuroendocrine tumors. The presence of a deficiency of MGMT, the drug-resistance gene, was associated with greater odds of an objective response (Abstract 4004).
Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Michael S. Hofman, MBBS, of Peter MacCallum Cancer Centre, University of Melbourne, discuss follow-up results on LuPSMA vs cabazitaxel in patients with metastatic castration-resistant prostate cancer progressing after docetaxel treatment. The findings suggest that LuPSMA is a suitable option for this population, with fewer adverse events, higher response rates, improved patient-reported outcomes, and similar overall survival compared with cabazitaxel (Abstract 5000).
Lisa A. Carey, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center, and Hope S. Rugo, MD, of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discuss phase III results from the TROPiCS-02 trial. This study showed that sacituzumab govitecan-hziy was more beneficial than single-agent chemotherapy in terms of progression-free survival in heavily pretreated patients with hormone receptor–positive/HER2-negative and unresectable advanced breast cancer (LBA1001).
Shilpa Gupta, MD, of the Cleveland Clinic Foundation, discusses an updated consensus definition for standard therapy and clinical trial eligibility for patients with metastatic urothelial cancer who are platinum-ineligible, criteria that are proposed to guide treatment recommendations for this population. This may be especially important now that the U.S. Food and Drug Administration has restricted the use of first-line pembrolizumab to those who are considered platinum-ineligible (Abstract 4577).
Karim Chamie, MD, of the University of California, Los Angeles, discusses final clinical results on combining the superagonist N-803 with bacillus Calmette-Guérin (BCG) in patients whose carcinoma in situ and high-grade non–muscle-invasive bladder cancers are unresponsive to BCG alone. Of note, cystectomy was avoided in more than 90% of patients with 2 years of follow-up (Abstract 4508).