By the time Patterns of Care study subjects were diagnosed in 2003, imatinib was standard first-line therapy for chronic myeloid leukemia, supplanting the existing standards of care9–12, 28
. Results from the analysis of three data bases included in this report indicate that increasing age was a barrier to receipt of imatinib therapy for chronic myeloid leukemia. Nearly 90% of Patterns of Care study subjects less than 60 years of age received imatinib. Although there was no significant difference in survival in these patients, it may be that the Patterns of Care study lacked the power to detect the difference with such a large percentage of patients on imatinib. Less than half of chronic myeloid leukemia patients 80 years of age and older received the drug. These results are disturbing because of the profound survival advantage accrued by the elderly Patterns of Care study subjects who received imatinib. Perhaps because of this, reductions in chronic myeloid leukemia mortality rates in the United States in recent years were most pronounced at younger ages and were least evident among the elderly.
Results from previous studies have shown that age can be a barrier to receipt of optimal treatment due, in part, to the presence of co-morbid conditions29–33
, increased toxicity of some therapies in the elderly29–34
, lack of data on the elderly from clinical trials35–38
, social marginalization30,31
, and patient and physician preferences31,32,39–41
. It is unlikely that co-morbid conditions influenced receipt of imatinib in the Patterns of Care study. Co-morbid conditions were documented here in similar proportions of those subjects who did and did not receive imatinib; this pattern persisted after adjustment for age at diagnosis.
It is possible that some prescribing physicians avoided imatinib therapy in elderly chronic myeloid leukemia patients out of concern for toxicity. Little toxicity was reported in clinical trials that established the efficacy of imatinib therapy for chronic myeloid leukemia 9–12
. It is possible that patients and physicians were unaware of such findings since results from clinical trials were often not reported by age. One study that specifically demonstrated the benefits of imatinib without significant toxicity in older chronic myeloid leukemia patients was published in 200328
. It is unlikely that those results were widely disseminated by the time most Patterns of Care study subjects were accrued. For these reasons, it is plausible that anxiety for, or lack of knowledge of, toxicity of imatinib therapy in the elderly could have contributed to the age disparity in treatment. Certainly, drug interactions with imatinib could be worse in the elderly, and this could also have been a limiting factor in physician decisions.
Imatinib use did not vary substantially by race/ethnicity, socioeconomic status, urban/rural residence, or insurance status; these findings persisted after adjustment for age at diagnosis. These findings suggest progress in the dissemination of novel cancer therapy since factors such as lower socioeconomic status, rural residency, and lack of insurance had previously influenced receipt of state-of-the-art cancer treatment30, 31
. Previous studies have shown that elderly patients generally do not perceive their age or current health as a barrier to treatment39,40,42
or as a limiting factor for their enrollment in clinical trials43
. Physician preferences for treatment may be influenced if elderly patients are perceived as less able to tolerate therapy or as having a short life expectancy, or if there is a dearth of clinical trial data specific to elderly patients39–41,44
Several limitations should be considered when interpreting results from this investigation. The study was based on a population-based sample that was generally representative of chronic myeloid leukemia cases diagnosed in participating SEER Program registries. Nonetheless, the sample size of 423 resulted in some analyses that were based on relatively few observations. For example, results regarding race/ethnicity and urban/rural residence should be interpreted with caution since the study sample included relatively few members of minority populations and rural residents. Indicators of socioeconomic status (i.e., income and education) were derived from aggregate measures that represented the census tract of residence for each Patterns of Care study subject. Nonetheless, previous studies have shown that such aggregate data can serve as reasonable surrogate measures of education and income18
. Finally, existing co-morbid conditions were documented from medical record review and physician statements, and were not categorized by severity. Indeed, ethical considerations may be important in the physician decision process for imatinib use in elderly with severe co-morbid conditions, such as dementia.
The high efficacy of imatinib resulted in dramatic increases in survival and diminished chronic myeloid leukemia mortality rates in the general population of the United States15–17
. However, results from this study also show that the percentage of chronic myeloid leukemia patients treated with imatinib declined with age. These findings indicate that age disparities in receipt of imatinib resulted in worse survival for many elderly chronic myeloid leukemia patients who might have benefited from this new therapy. Age disparities in treatment of cancer patients have been well-documented in the medical literature29–33
and a number of positive steps have been taken to address these concerns. For example, the FDA issued guidelines for the study of drugs likely to be used in the elderly45
, the National Cancer Care Network has issued guidelines for care of elderly cancer patients46,47
, and clinical trial groups have developed tools for uniformly evaluating elderly cancer patients48
. The present study serves as a reminder that these steps are not sufficient, and additional work is needed to ensure that novel therapy is available to all.
Patient advocates have challenged the status quo
of drug development and delivery49
, and there is undoubtedly a role for such advocacy in the dissemination of new cancer therapies. However, physicians must also bear responsibility for the dissemination of novel cancer therapy to elderly patients. Specifically, several further measures are recommended: 1) Mandatory inclusion of elderly patients in federally-funded clinical trials, 2) Requiring separate reporting of study results for elderly patients, and 3) Implementing standards that require pharmaceutical firms to educate oncologists regarding the safety and efficacy of novel therapy in the elderly. In summary, age is a major health disparity when it comes to the introduction of novel cancer therapy, and this disparity results in mortality that could be prevented.