Patient feedback can help ensure balance between cancer treatment efficacy, tolerability
Researchers have launched a research consortium that they hope will identify efficient methods to incorporate patient-reported outcomes into clinical trials of experimental cancer treatments.
The investigators will analyze data from three prior trials conducted through the National Surgical Adjuvant Breast and Bowel Project, as well as three ongoing immunotherapy trials, to create new statistical measurement criteria that will help assess how well trial participants tolerate treatment.
A “pressing need” exists to incorporate patient feedback into tolerability and toxicity evaluations of new cancer treatments, according to study co-leader André Rogatko, PhD, director of the Biostatistics and Bioinformatics Research Center at Cedars-Sinai.
The toxicity and tolerability information that clinicians collect may show no difference between multiple equally efficacious treatments. However, patient-reported outcomes can offer insights into important variations.
“It’s becoming more important to incorporate that potentially differing information into decisions about which therapy or which dose should be given,” Rogatko told HemOnc Today. “This will help personalize the treatment and find a better balance between efficacy and tolerability.”
Rogatko is co-leading the study with Patricia A. Ganz, MD, professor of medicine at David Geffen School of Medicine at UCLA and director of the Center for Cancer Prevention & Control Research at Jonsson Comprehensive Cancer Center.
Researchers will use a toxicity index Rogatko previously developed, as well as NCI’s Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE), a validated measurement system designed to characterize frequency, severity and impact of 78 symptomatic treatment toxicities, including pain, nausea, fatigue and cutaneous side effects.
“A big unknown is how adverse events affect patients over longer periods of time — particularly in immunotherapy, in which we only recently are learning about long-term toxicity and how it affects quality of life," Rogatko said.
HemOnc Today spoke with Rogatko about how this research effort came about, the timeline for results, and the implications the findings may have on treatment development and patient quality of life.
Question: What prompted this study?
Answer: There is an inherent strain between trying to help a patient with particular treatments and the adverse events that can result from them. Trying to develop methods that summarize this tug and make that information more readily available has been an interest of mine for a long time. The NCI invested substantial resources creating questionnaires that allow patients to report their experiences with treatment, but there are not many methods through which these data can be analyzed. We want to address how that information can be added to what clinicians traditionally see, while using this knowledge to help improve patients’ quality of life.
Q: To what extent is the patient’s voice included now, and how are patient-reported events measured?
A: There is some disconnect between what a patient feels and what the patient reports, or what the clinician perceives. When patients talk with their physicians, they often try to minimize any negative effects. This downplaying of pain seems to be part of human psychology. We want to know how to capture what the patient is experiencing in a more accurate way so this information can help influence treatment decisions.
Q: How are you conducting this analysis?
A: The goal is to develop tools to express treatment-related adverse events and incorporate patient perceptions into that. A clinical trial can have up to 12,000 pieces of information about toxicities experienced by patients. Oftentimes, the most severe adverse events are reported but everything else goes unreported. Our goal is to summarize all of this information so it accurately reflects each patient’s experience and then compares that experience with those of other patients.
As each trial ends, our primary focus will be to make sure more statistics are described as treatment continues. If a patient has a grade 2 toxicity, that is not always a big problem. But if someone has grade 2 toxicity for 5 years, that can be a very big problem. That aspect of variability has not been addressed by clinical trial methods so far.
We previously developed a summary measure, the toxicity index, to discriminate patients based on their overall toxicity experiences. Toxicity data are summarized for each subject from graded symptomatic adverse events according to CTCAE. The toxicity index accounts for all observed toxicity grades rather than only the most severe one, as is conventionally done. Because of its sensitivity to differences in the overall toxicity, the toxicity index is likely to be useful also for identifying predictors of treatment-related toxicity. We will employ the toxicity index and extensions or refinements of it to support new and improved methods for patient-reported outcomes and related adverse event data.
Although we will focus much effort on developing new technical statistical methods, we will work as a team of patient-reported outcome experts, oncologists, data scientists and clinical trial experts to keep the developments grounded in patient-centric and clinical trial relevant perspectives. The clinical trial data we will examine come from several kinds of treatments and cancer sites, but with an emphasis on immunotherapy for our PRO-CTCAE trials, in anticipation of the importance of this class of agents for the near future. All our methods and results will be made available to other funded teams on an ongoing basis, and we also expect to derive help from their progress using a collaborative model.
Q: Can you describe the patient populations of the trials you are analyzing?
A: As general as statistics and methods are, the patient population of a particular trial is almost irrelevant for our purposes. No matter if a person has early-stage or late-stage cancer, there will be some toxicity associated with treatment. We are measuring the occurrence of that toxicity and hopefully will be able to use our data to find a better combination of therapies that can maximize treatment efficacy, minimize toxicity and increase quality of life.
Q: What do you consider the greatest potential implication of your results?
A: Our goal is to make sure that the patient’s voice is heard, and that it will have an impact on the treatment and the decision of selecting a particular treatment. It is a very exciting idea that decisions are meant to be made not only by clinicians observing the patient, but by the patients themselves. – by Joe Gramigna
For more information:
André Rogatko, PhD, can be reached at Cedars-Sinai Samuel Oschin Comprehensive Cancer Center, 116 N. Robertson Blvd., Suite 900C, Los Angeles, CA 90048; email: firstname.lastname@example.org.
Disclosure: The NCI provided funding for this study. Rogatko reports no relevant financial disclosures.