The number of older patients with cancer is increasing as a result of the ageing of Western societies. Immune checkpoint inhibitors have improved cancer treatment and are associated with lower rates ...of treatment-related toxicity compared with chemotherapy in the general population. Nonetheless, immune checkpoint inhibitors have potentially serious immune-related adverse events, which might have a greater impact on older and more vulnerable patients and potentially influence treatment efficacy and quality of life. Previous clinical trials have shown no major increase in immune-related adverse events; however, older patients are underrepresented and relatively healthy in these trials. Observational studies suggest that older and more vulnerable patients may be at a higher risk of immune-related adverse events and early treatment discontinuation. Geriatric assessment could help identify older patients who will benefit from immune checkpoint inhibitors.
Studies on new anticancer drugs often inappropriately conclude that these treatments are well tolerated and feasible in the older population with cancer, despite the drug being investigated in only a ...selection of healthy older patients who are not representative of the true older population. In this Personal View we outline examples of reports that provide misleading information to clinicians, mostly because the tolerance and efficacy were not assessed according to frailty status and only a few people who are frail were included. We also provide solutions on how to inform clinicians, patients, and health authorities more clearly about the benefits and disadvantages of new and upcoming anticancer drugs for older people with cancer.
Background
Studies have demonstrated worse breast cancer‐specific mortality with older age, despite an increasing risk of dying from other causes due to comorbidity (competing mortality). However, ...findings on the association between older age and recurrence risk are inconsistent. The aim of this study was to assess incidences of locoregional and distant recurrence by age, taking competing mortality into account.
Materials and Methods
Patients surgically treated for nonmetastasized breast cancer between 2003 and 2009 were selected from The Netherlands Cancer Registry. Cumulative incidences of recurrence were calculated considering death without distant recurrence as competing event. Fine and Gray analyses were performed to characterize the impact of age (70–74 reference group, 75–79, and ≥80 years) on recurrence risk.
Results
A total of 18,419 patients were included. Nine‐year cumulative incidences of locoregional recurrence were 2.5%, 3.1%, and 2.9% in patients aged 70–74, 75–79, and ≥80 years, and 9‐year cumulative incidences of distant recurrence were 10.9%, 15.9%, and 12.7%, respectively. After adjustment for tumor and treatment characteristics, age was not associated with locoregional recurrence risk. For distant recurrence, patients aged 75–79 years remained at higher risk after adjustment for tumor and treatment characteristics (75–79 years subdistribution hazard ratio sHR, 1.25; 95% confidence interval CI, 1.11–1.41; ≥80 years sHR, 1.03; 95% CI, 0.91–1.17).
Conclusion
Patients aged 75–79 years had a higher risk of distant recurrence than patients aged 70–74 years, despite the higher competing mortality. Individualizing treatment by using prediction tools that include competing mortality could improve outcome for older patients with breast cancer.
Implications for Practice
In this population‐based study of 18,419 surgically treated patients aged 70 years or older, patients aged 75–79 years were at higher risk of distant recurrence than were patients aged 70–74 years. This finding suggests that patients in this age category are undertreated. In contrast, it was also demonstrated that the risk of dying without a recurrence strongly increases with age, and patients with a high competing mortality risk are easily overtreated. To identify older patients who may benefit from more treatment, clinicians should therefore take competing mortality risk into account. Prediction tools could facilitate this and thereby improve treatment strategy.
Evidence suggests that age is an independent risk factor for worse breast cancer outcome. This study assessed the incidence of locoregional and distant recurrence by age at diagnosis among patients aged ≥70 years, while taking competing mortality risks into account.
An important consideration in studies that use cause-specific endpoints such as cancer-specific survival or disease recurrence is that risk of dying from another cause before experiencing the event ...of interest is generally much higher in older patients. Such competing events are of major importance in the design and analysis of studies with older patients, as a patient who dies from another cause before the event of interest cannot reach the endpoint. In this Commentary, we present several clinical examples of research questions in a population-based cohort of older breast cancer patients with a high frequency of competing events and discuss implications of choosing models that deal with competing risks in different ways. We show that in populations with high frequency of competing events, it is important to consider which method is most appropriate to estimate cause-specific endpoints. We demonstrate that when calculating absolute cause-specific risks the Kaplan-Meier method overestimates risk of the event of interest and that the cumulative incidence competing risks (CICR) method, which takes competing risks into account, should be used instead. Two approaches are commonly used to model the association between prognostic factors and cause-specific survival: the Cox proportional hazards model and the Fine and Gray model. We discuss both models and show that in etiologic research the Cox Proportional Hazards model is recommended, while in predictive research the Fine and Gray model is often more appropriate. In conclusion, in studies with cause-specific endpoints in populations with a high frequency of competing events, researchers should carefully choose the most appropriate statistical method to prevent incorrect interpretation of results.
Introduction
Since older patients with breast cancer are underrepresented in clinical trials, an oncogeriatric approach is advocated to guide treatment decisions. However, the effect on outcomes is ...unclear. The aim of this study was to compare treatments and outcomes between patients treated in an oncogeriatric and a standard care setting.
Methods
Patients aged ≥ 70 years with early stage breast cancer were included. The
oncogeriatric cohort
comprised unselected patients from the Moffitt Cancer Center, and the
standard cohort
patients from a Dutch population-based cohort. Cox models were used to characterize the influence of care setting on recurrence risk and overall mortality.
Results
Overall, 268 patients were included in the oncogeriatric and 1932 patients in the standard cohort. Patients in the oncogeriatric cohort were slightly younger, had more comorbidity, and received more adjuvant endocrine therapy and chemotherapy. Oncogeriatric care was associated with a lower risk of recurrence, which remained significant after adjustment for patient and tumour characteristics hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.44–0.99. Oncogeriatric care was also associated with a lower overall mortality, which also remained significant after adjustment for patient and tumour characteristics (HR 0.69, 95% CI 0.55–0.87).
Conclusions
Patients treated in the oncogeriatric care setting had a lower risk of recurrence, which may be explained by more systemic treatment. Overall mortality was also lower, but other explanations besides care setting could not be ruled out as the cohorts had different patient profiles. Future studies need to clarify the impact of an oncogeriatric approach on outcomes.
There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older ...patients with breast cancer within the first 5 years after diagnosis.
Women aged ≥70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up.
In total, 299 patients were included (mean standard deviation (SD) age: 75.8 5.2 years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had significant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had similar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002).
Depression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms.
•Depression, loneliness and apathy are common in older women with breast cancer.•Adjuvant systemic therapies were not associated with worse mental health outcomes.•Frailty exacerbates depressive symptoms, loneliness and apathy.
Purpose
Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of ...adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL).
Methods
Patients aged ≥ 70 years with stage I–III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time.
Results
Overall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (
b
= − 4.37; 95% CI − 7.96 to − 0.78;
p
= 0.017) over the first 2 years, in particular on the future perspective subscale (
b
= − 11.10; 95% CI − 18.80 to − 3.40;
p
= 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement.
Conclusion
A large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy.
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