This year saw a "premiere" in global demographic development: the number of people over 65 outpaced the number of people under 5 for the first time. The incidence of many diseases, including cancer, is likely to increase dramatically.
However, "older" patients are clearly under-represented in clinical trials. Data from a recent abstract (source 1) submitted to ASCO 2019 confirm this: the proportion of patients over 65 years of age in Phase III trials over the last 10 years was 10-40%. The source was 201 studies on three common solid tumors and three hematologic neoplasia. Patients over 65 years of age accounted for just 15% of breast cancer and 29% of colon cancer.
The transferability of the results of clinical trials in younger adults to the older patient population seems questionable. The editorial of the July issue of Lancet Oncology discusses precisely this paradox (source 2).
It is often the case that comorbidities thwart the inclusion of patients over 65 in oncological studies. However, in addition to clinical factors, non-clinical factors also play a role. For example, an exciting study published in the Journal of the American Medical Association (source 3) shows that the discrepancy between the study world and the real patient world with regards to age composition is greater in industry-sponsored studies and studies on "targeted therapies" than in independent studies. Such a bias could promote more positive study results. The data come from more than 263,000 patients from 302 randomized clinical trials. Overall, the study populations were significantly younger than the typical patient populations (ordered by disease localization).
In addition to the age limit - as the editorial argues - the majority of studies also have the effect that study participants are often fitter and have fewer concomitant diseases than the general population - even if they are cancer patients. Such patients may also sometimes be better educated and of higher socioeconomic status. The Lancet editorial also poses the question: "If patients are so stringently selected for study participation, are the study populations still representative?”
Regarding the problem of increasing incidences of colorectal cancer in younger adults, recent studies indicate the average onset of the disease is 68 years for men and 72 years for women. The frequently drawn upper limit of 65 years can, therefore, lead to the exclusion of many diagnosed cases. What remains is an atypical population with earlier onset of the disease - and possibly also more aggressive progressions. Therapies developed in such populations may not be suitable for older patients. The solution would be simple: Inclusion criteria for age studies should depend on the tumor entity.
Clinicians are increasingly considering in their decisions that numerical age is not a reliable measure of a patient's state of health. Geriatric assessment tools to determine functional age, or guidelines focused on the needs of this population can help, such as those of the International Society of Geriatric Oncology.
People beyond a certain age are easily perceived as weak or frail per se. But diseases and severe physical or mental deterioration should not actually be "normal" or compelling side effects of aging.
Sources:
1. Swathi Gopishetty, Vamsi Kota, Achuta Kumar Guddati; Navicent Health, Macon, GA; Winship Cancer Institute of Emory University, Atlanta, GA; SUNY Downstate Medical Center, Brooklyn. Analysis of proportion of geriatric patients in phase III cancer clinical trials. Meeting Abstracts Available at: http://abstracts.asco.org/239/AbstView (Accessed: 6th July 2019)
2. Oncology, T. L. Not old, just older: considering age in cancer care. The Lancet Oncology 20, 887 (2019).
3. Ludmir, E. B. et al. Factors Associated With Age Disparities Among Cancer Clinical Trial Participants. JAMA Oncol (2019). doi:10.1001/jamaoncol.2019.2055