How do you, as a clinician, decide how to treat a patient with cancer when the patient sitting in front of you does not look anything like the patients in the clinical trials that have established the efficacy of the known treatments for that cancer? Research shows that two of every three new cancers occur in older adults, yet these older adults only account for 30 percent of clinical trial enrollment, Gabrielle Rocque, MD, Assistant Professor of Medicine in the Division of Hematology & Oncology at the University of Alabama at Birmingham (UAB), and Grant Williams, MD, Assistant Professor at The Institute for Cancer Outcomes and Survivorship at UAB, noted in an editorial (J Clin Oncol 2019; doi: 10.1200/JCO.19.02588).
In the editorial, the coauthors argue that clinicians need more evidence when it comes to making decisions about how to treat older adults with cancer. More evidence from clinical trials, they note, would be ideal; but in the absence of those studies, other steps can be taken to learn from cancer databases and to better understand patients' unique preferences about treatment that could impact treatment decisions.
"Right now we are in a data-free zone. And in many cases, we don't have any data on frail older adults. That's a particular population that is vulnerable and may in fact not be appropriate to give the most intense chemotherapy regimens," Rocque told Oncology Times. "But we don't know because those studies haven't been done to say how should frailty impact decision-making."
The data-free zone means these patients are at risk of both being undertreated and of being overtreated, she said.
The editorial accompanies a report by a group of FDA researchers that evaluated the efficacy of a group of targeted therapies in older women for the treatment of metastatic breast cancer (J Clin Oncol 2019; doi: 10.1200/JCO.18.02217). Here's what else Rocque says about the editorial.
1. Your editorial refers to a study that looked at the efficacy of novel targeted agents in treating older women with breast cancer compared with younger women. Why was this study so significant to the points you make in the editorial?
"For this editorial, we started by reviewing the manuscript and saw that the researchers had done an excellent job of really thinking about how older adults are doing with this particular class of drugs [CDK4/6 inhibitors and aromatase inhibitors].
"They highlighted the efficacy benefits that were seen in older adults. At the same time, there was definitely a decline in the patients' functional status. The message of my editorial is that we should look, not only at efficacy outcomes, but also other patient outcomes, like functional status, which are really important factors that older adults, and frankly all patients, consider when making decisions.
"We have a real need to fill in this evidence gap because we care for a lot of older adults and we don't have great data, not only on efficacy, but also on how treatments are impacting things that are important to them.
"I, as a clinician, work with metastatic breast cancer patients and have done a fair amount of research in terms of preferences in decisions. We've seen that individual patients' preferences often include many different facets of life beyond what we typically think about as physicians, which is how effective is this drug in controlling the growth of the cancer, what are the potential toxicities, and what are the costs.
"Patients are also considering [things like] the impact on their functional status, how is this going to impact their families, are they going to be a burden on their families, and what are the implications for their emotional state.
"So this to me provided a great opportunity to highlight that we don't enroll older adults in clinical trial as much as we should, which leads to an evidence gap. Without good data, people will often do things that aren't evidence-based in terms of reducing the intensity of treatment without having the evidence to back that up."
2. What needs to change and what are the next steps to initiating these shifts?
"An optimal approach is doing more studies that are specifically looking at older adults-and really including all of these measures, like frailty and geriatric assessment.
"A second level is making sure that we are promoting enrollment of older adults into our regular clinical trials. And I think that is something that is very actionable that we really need to work on.
"And I think the third level is conducting analyses in population-level, real-world data, such as using some of the newer electronic databases like ASCO's CancerLinQ and Flatiron. These types of analyses can be done to understand what are the practice patterns and outcomes for populations that are not well-represented in clinical trials.
"One approach is relaxing some of the eligibility criteria [for clinical trials]-so actually including patients with comorbidities because that is what we see in a general practice.
"I also think there needs to be more support infrastructure for educating both the patients and the clinicians about the importance of including older adults in clinical trials. Additional work needs to be done to understand what are the barriers [that] prevent older adults from participating."
3. What is the bottom-line takeaway message?
"Number one, we need to evaluate outcomes for older adults with cancer, and as practicing clinicians really have an understanding when you are applying clinical trial results to populations that aren't well-represented who were included in the trial and how that might differ from the patients sitting in clinic. And to that end, having clinicians referring older adults to trials is really important.
"And finally, I think it is incredibly important to ask patients what's important to them. And for clinicians in an area where we don't have perfect evidence, I think it's incredibly important to understand what is the patient hoping for out of their treatment and what are the aspects of their life that are particularly important to their quality of life-and really think about how the treatments we're delivering align with those preferences."