Geriatric oncology field ‘entering into adulthood’
Addressing inequities in health care has become a priority across all branches of medicine, including oncology.
For the field of geriatric oncology — which, along with the population of Americans aged 65 years or older, has grown rapidly during the past decade — eliminating gaps in research that may negatively impact care of older adults with cancer remains a pivotal challenge.
Source: Craig Takahashi / City of Hope.
“Older adults with cancer are not included in clinical trials that provide us with adequate safety and efficacy data, and the older adults who are included tend to be the most fit,” Supriya Gupta Mohile, MD, MS, Wehrheim professor of medicine at University of Rochester, told Healio | HemOnc Today. “Older adults who have other medical problems are not represented in clinical trials, and this is a key gap in care. As the clinicians who are seeing these adults in clinic and extrapolating data on safety and efficacy, we cannot tell our patients what the likelihood of coming through an intense curative-intent treatment will be because we do not have the data. It simply does not exist.”
The dearth of clinical trial data has not stopped researchers from investigating geriatric assessment-guided interventions, which have shown promise for reducing treatment-associated toxicities among older adults with cancer, as well as improving their quality of life and conversations about aging-related concerns.
“We are now seeing the first hints from large, randomized studies that show how to intervene, and the interventions that we are developing are largely multidisciplinary team interventions that include not only physicians but also nurses, social workers and physical therapists. We now know that this helps to reduce treatment-associated toxicity and improve conversations,” William Dale, MD, PhD, director of the Center for Cancer and Aging and professor and chair of the department of supportive care medicine at City of Hope, told Healio | HemOnc Today.
However, use of geriatric assessment — recommended in a 2018 ASCO guideline for all patients aged 65 years or older who receive chemotherapy — has been limited mostly to major cancer centers with geriatric oncology programs.
“Only 25% of oncology practices say they perform geriatric assessment among their older adult patients,” Dale said. “How do we build the assessment into workflows so that it does not add excessive time — either by having nonclinicians do it or by having patients and families do it as part of the intake process — and how extensive do the assessments need to be to be effective? We know that performance status (eg, Karnofsky performance or ECOG) does not predict these outcomes like the full geriatric assessment does. So, how brief can we make the geriatric assessment so that it is still effective and does not take up so much time is the big implementation question that we need more research to answer.”
Healio | HemOnc Today spoke with geriatric oncologists and geriatricians about the lack of data on older adults with cancer, efforts to increase clinical trial participation among this patient population, the value of geriatric assessments and how community oncology clinics can implement them, and current therapeutic research in this space.
Underrepresentation in trials
Clinical trial participation among older adults with cancer falls significantly below the percentage of older adults who have cancer.
“A recent analysis by the FDA found that only 24% of patients enrolled in trials supporting oncology-drug approvals were 70 years of age and older compared with 42% of such patients in the SEER database who would be eligible to receive the treatments after they are approved,” Monica M. Bertagnolli, MD, surgical oncologist at Dana-Farber Cancer Institute, and Harpreet Singh, MD, oncologist at the FDA, wrote in an editorial published last year in The New England Journal of Medicine. “Most trials also had exclusion criteria preventing all but the fittest older adults from participating.”
The underrepresentation of older patients with cancer in randomized clinical trials of new therapies and treatment combinations reflects a need for more work to improve access, Martine Extermann, MD, PhD, leader of the senior adult oncology program at Moffitt Cancer Center, told Healio | HemOnc Today.
“Clinical trial participation among older adults with cancer has not changed a whole lot within the last decade. We need to keep pushing to broaden the inclusion criteria,” Extermann said. “There has been some modernization of inclusion criteria, with many studies now having creatinine clearance of 30 mL/min instead of 60 mL/min, which is helpful for older patients who often have moderate dysfunction. We need to continue in that vein to ensure that studies are more accessible to our older patients.”
This said, a large group of older patients with extensive comorbidities and/or issues with drug interactions will never be included in clinical trials, Extermann added.
“There is a big opportunity here for machine learning and big data to try and leverage that into making it a real clinical consultation so that we can learn from real-world evidence and develop medications for the group of older patients who will never be on clinical trial,” she said.
As the number of older Americans has increased, so have efforts to ensure they are included on cancer clinical trials.
“There is an awareness now that older adults are vulnerable and underrepresented. An increasing group of investigators around the country are working to build clinical trials dedicated to these patients,” Rachel A. Freedman, MD, MPH, medical oncologist and geriatrics-focused researcher in the breast oncology center at Susan F. Smith Center for Women’s Cancers and senior physician at Dana-Farber Cancer Institute, told Healio | HemOnc Today. “There is a lot of movement on the federal level and organizational level to fund research in the area of cancer in older adults. There is also a lot of forward thinking on how we can better design clinical trials in general, to ensure that eligibility requirements are as open as possible, without upper-age limits, and with more allowance of those who have other chronic medical conditions. There is a lot going on in this space, but we of course always need more funding and focus. It will take time to get all the answers that we need, because answering these important questions takes years.”
Increasing trial access
Many scientific groups are working diligently to find those answers, according to Mohile.
Mohile and Diane St. Germain, RN, MS, CRNP, of NCI’s Community Oncology and Prevention Trials Research Group, co-led a workshop last year with multiple stakeholders to discuss ways to increase accrual of older adults onto NCI-funded clinical trials.
Actions recommended during the forum included:
- loosening clinical trial eligibility criteria, including restrictions on creatinine clearance and presence of other active cancer;
- providing support for community oncology offices so they can participate in clinical research; and
- designing trials specifically for older adults with cancer.
“Often, kidney function and/or comorbidity restrictions are cut and pasted from protocol to protocol. As a result, people who have a little bit of kidney function restriction cannot go on a trial that wouldn’t impact the drug being studied,” Mohile said. “There are also patients who have low-grade cancers and develop a new cancer but cannot go on clinical trials because of eligibility, but the older someone gets, the more likelihood that they have had more than one cancer.”
Clinical trials also must be accessible to all patients, whether in rural areas or community oncology offices, Mohile added.
“We need to provide support to those clinics to conduct this type of research. These are the things that need to be overcome, and there are ways to do this,” Mohile said.
One way would be to create networks that provide community oncology practices with the necessary infrastructure to enroll patients onto trials, according to Mohile.
“The Wilmot Cancer Institute has a network of community oncology clinics, and we have developed infrastructure to open trials in several of those clinics,” she said. “The community oncologist can offer our trials to their older adults with cancer. Also, education for investigators not only when they are designing trials but also during the review processes is important. There should be people during that process who ensure that eligibility criteria make sense for each clinical trial. More flexibility is needed in eligibility.”
Investigators also need to work with caregivers and patients throughout the research design process to ensure that what they measure is relevant to the populations studied, Mohile added.
“Historically, we have looked at response rates and survival, but my older adults tell me they care about functional independence, their memory and not making other medical problems worse,” Mohile said. “We should be collecting those as outcomes, too, rather than just the traditional outcomes.”
Geriatric assessments
Geriatric assessments have provided insights into many domains not typically covered in routine oncology evaluations. The assessments measure the functional, psychological, physical and cognitive abilities of older adults in addition to their comorbidities and medication use.
Interventions guided by these assessments have shown benefit among older adults with cancer.
In the GAIN study, Dale and colleagues randomly assigned patients aged 65 years and older with solid malignant neoplasms to either a geriatric assessment-driven intervention — including a geriatrics-trained nurse practitioner and a multidisciplinary team that reviewed geriatric assessment results and implemented interventions based on prespecified thresholds — or to standard of care that consisted of geriatric assessment results sent to treating oncologists for consideration.
Results showed incidence of grade 3 or higher chemotherapy-associated toxicities was 50.5% among patients in the geriatric-assessment-driven intervention group compared with 60.6% among older adults assigned standard of care.
“We are still figuring out how to use the information from the GAIN study and others like GAP70+, which is one of the scientific gaps to be filled,” Dale said. “The other important gap is the evidence, data and confidence we have that these interventions work is based mostly on studies conducted at large cancer centers and in large research networks, so we need to know how they work in the community setting, where at least 75% of patients are receiving cancer treatment. That is the next big hurdle to overcome.”
The GAP70+ trial showed a geriatric intervention for older patients with advanced cancer reduced serious treatment-associated toxicities.
The study enrolled 718 patients (mean age, 77.2 years; 57% men) across 40 community oncology practice clusters in the U.S. Researchers randomly assigned the clusters to an intervention in which oncologists received a tailored geriatric assessment summary and management recommendations or to a usual care group with no geriatric assessment summary or management recommendations provided to oncologists.
“We trained the teams at the sites that were randomized to the intervention and at those sites, enrolled patients received a printout of the geriatric assessment results plus a list of recommendations of interventions based on those results,” Mohile said “We did not tell the oncologists what they had to do, we just gave them the information because they are in charge of their patients and they know their patients best. We gave oncologists autonomy in what they implemented, but the majority reduced the treatment dosing at the first cycle for patients they thought were frail and also implemented interventions to help with outcomes.”
Results showed 51% of patients assigned to the intervention group had grade 3 to grade 5 adverse events vs. 71% of patients assigned to usual care (RR = 0.74; 95% CI, 0.64-0.86). In addition, patients assigned the intervention had fewer falls over 3 months (12% vs. 21%; RR = 0.58; 95% CI, 0.4-0.84) and more medications discontinued (mean adjusted difference, 0.14; 95% CI, 0.03-0.25).
“Ultimately, we found that the sites that were randomized to the intervention, through better decision-making for treatment and intervention, had significantly less toxicity overall and less falls and overall improved polypharmacy,” Mohile said.
Geriatric assessments have shown benefit in other areas, as well.
In a study presented at the 2018 ASCO Annual Meeting, Mohile, Dale and colleagues found use of geriatric assessments during routine care of older individuals with advanced cancer significantly improved physician-patient communication about age-related concerns.
The study included 541 patients (mean age, 77 years; 49% women) with incurable advanced solid tumors or lymphoma. The patients underwent geriatric assessment and received treatment between 2014 and 2017 at one of 31 community oncology practices affiliated with University of Rochester’s NCI Community Oncology Research Program. Researchers randomly assigned these practices to a geriatric assessment group or usual-care group.
Results showed physicians with a practice in the intervention group conducted a mean 3.5 (95% CI, 2.28-4.72) more discussions about age-related concerns during clinic visits than physicians with a practice in the usual-care group. In the geriatric assessment group, an average of two (95% CI, 1.2-2.69) more conversations had higher quality communication and 1.9 (95% CI, 1.14-2.73) more led to interventions.
“Our health care system is busy, and we know that takes more time to think through these assessment results as busy oncologists,” Mohile said. “It takes a champion to get people to organize to do the assessment, and there is movement toward implementation science and partnering with implementation scientists to understand the best workflows for geriatric assessment to especially make it happen in community oncology clinics.
“My colleague, Lisa Lowenstein PhD, MPH, and I recently received funding from the Patient Centered Outcomes Research Institute to look at how to best implement geriatric assessment across community oncology sites. We will be working with five networks of community oncology sites across the country to conduct interviews with staff, develop workflows with them, study how they implement the assessment and assess barriers to implementation, as well as provide solutions,” Mohile added. “We will be working with Association of Community Cancer Centers to assimilate the information to community oncology clinics across the country.”
New and ongoing research
New and ongoing research reflect efforts to address gaps in treatment for older adults with cancer.
In the ongoing GIANT trial, researchers are assessing gemcitabine and nab-paclitaxel vs. 5-FU and liposomal irinotecan among older patients with treatment-naive metastatic pancreatic cancer.
“These patients have some geriatric limitations, which is why I am very glad to see this type of therapy being studied now in cooperative groups for this population,” Extermann said. “My hope is that we will see more studies like this that address older patients with some limitations.”
Results of another study, presented at last year’s International Association for the Study of Lung Cancer World Conference on Lung Cancer, showed older patients with late-stage non-small cell lung cancer appeared to benefit from immunotherapy.
As Healio | HemOnc Today previously reported, the analysis included 24,136 patients aged 75 years or older (immunotherapy, n = 2,241; no immunotherapy n = 21,895) and 62,037 patients aged younger than 75 years (immunotherapy, n = 8,968; no immunotherapy, n = 53,069) with stage IV NSCLC treated between 2014 and 2015.
Univariate analysis showed a survival benefit with immunotherapy among patients aged 75 years or older (median OS, 11.9 months vs. 5.4 months; HR = 0.61; 95% CI, 0.58-0.64), as well as among those aged younger than 75 years (median OS, 14.5 months vs. 7.8 months; HR = 0.67; 95% CI, 0.65-0.68).
Dale, Mohile and Paul B. Jacobsen, PhD, associate director of NCI’s division of cancer control and population science, included articles on therapeutic options, aging-specific treatment concerns, and assessment and intervention options for older adults in a special series published in Journal of Clinical Oncology.
“We spent a lot of time showing people that geriatric assessments work, why they are important, and that we can make a difference by using them. We are also updating guidelines. Everyone finally agrees that it is the right thing to do and now we are trying to figure out exactly what we should do and how to do it,” Dale said. “Our population is getting older, most patients with cancer are aged older than 65 years, and we are all going to have to deal with this. There are not enough geriatricians in the world to do this.”
Nevertheless. Dale said he is optimistic.
“Our geriatric oncology research group CARG (mycarg.org) started with 10 people in 2006 and now includes well over 450 people who want to do research in the older adult population,” he said. “We are entering into adulthood for our field and we are in a great place. I once felt knew everything in the field, but I can no longer keep track of how much work is going on — and that is a good sign. We need more oncologists in general to take on this aging component of care. The next 5 to 10 years will see the field of elderhood essentially become regarded like other fields in oncology.”
- References:
- Bertagnolli MM, et al. N Engl J Med. 2021;doi:10.1056/NEJMp2106089.
- Dale W, et al. J Clin Oncol. 2021;doi:10.1200/JCO.21.00887.
- Li D, et al. JAMA Oncol. 2021;doi:10.1001/jamaoncol.2021.4158.
- Mohile SG, et al. J Clin Oncol. 2018;doi:10.1200/JCO.2018.78.8687.
- Mohile SG, et al. Abstract LBA10003. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
- Mohile SG, et al. Lancet. 2021;doi:10.1016/S0140-6736(21)01789-X.
- Takamori S, et al. Abstract MA15.07. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer (virtual meeting); Sept. 8-14, 2021.
- For more information:
- William Dale, MD, PhD, can be reached at City of Hope, 1500 E. Duarte Road, Duarte, CA 91010; email: wdale@coh.org; Twitter: @WilliamDale_MD.
- Martine Extermann, MD, PhD, can be reached at Moffitt Cancer Center, Richard M. Schulze Family Foundation Outpatient Center at McKinley Campus, 10920 N. McKinley Drive, Tampa, FL 33612; email: martine.extermann@moffitt.org.
- Rachel A. Freedman, MD, MPH, can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215; email: rachel_freedman@dfci.harvard.edu.
- Supriya Gupta Mohile, MD, MS, can be reached at University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14642; email: supriya_mohile@urmc.rochester.edu.
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