Cancer incidence increases with age, and as life expectancy increases, the number of elderly patients with cancer is increasing. Cancer treatments, including chemotherapy and radiotherapy, have ...significant short- and long-term effects on cardiovascular function. These cardiotoxic effects can be acute, such as changes in electrocardiogram (ECG), arrhythmias, ischemia, and pericarditis and/or myocarditis-like syndromes, or they can be chronic, such as ventricular dysfunction. Anticancer therapies can also have indirect effects, such as alterations in blood pressure, or can cause metabolic abnormalities that subsequently increase risk for cardiac events. In this review, we explore both observational and clinical trial evidence of cardiac risk in the elderly. In both observational and clinical trial data, risk of cardiotoxicity with anthracycline-based chemotherapy increases with age. However, it is less clear whether the association between age and cardiotoxicity exists for newer treatments. The association may not be well demonstrated as a result of under-representation of elderly patients in clinical trials and avoidance of these therapies in this population. In addition, we discuss strategies for surveillance and prevention of cardiotoxicity in the elderly. In the elderly, it is important to be aware of the potential for cardiotoxicity during long-term follow-up and to consider both prevention and surveillance of these late effects.
Background
Survival outcomes in metastatic breast cancer (MBC) have improved due to novel agents such as CDK4/6 inhibitors (CDK4/6i). Nevertheless, Black patients and patients with lower ...socioeconomic status (SES) continue to bear a disproportionate mortality burden.
Methods
We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database (FHD). A dataset was constructed to include Black/African-American (Black/AA) and White patients with hormone receptor (HR)-positive, HER2-negative MBC. Outcomes included CDK4/6i use (overall and first-line), and rates of leukopenia, dose reduction, and time on treatment for first-line CDK4/6i. Multivariable logistic regression was used to evaluate factors associated with use and outcomes.
Results
A total of 6802 patients with MBC were included, of which 5187 (76.3%) received CDK4/6i. Of those, 3186 (61.4%) received CDK4/6i first-line. Overall, 86.7% of patients were categorized as White and 13.3% as Black/AA; 22.4% were > 75 years old; 12.6% were treated at an academic site; 3.3% had Medicaid insurance. In addition to advanced age and poorer performance status, lower use of CDK4/6i was associated with Black/AA vs White race (72.9% vs 76.8%; OR 0.83, 95% CI 0.70–0.99, p = 0.04) and Medicaid vs commercial insurance (69.6% vs 77.4%; OR: 0.68, 95% CI 0.49–0.95, p = 0.02). Odds of CDK4/6i use were twofold higher for patients treated at an academic center (p < 0.001). Rates of CDK4/6i-induced leukopenia and dose reductions did not differ significantly by race, insurance type, or treatment site. Time on CDK4/6i was significantly lower among Medicaid patients (395 days) than patients with commercial insurance (558 days) or Medicare (643 days) (p = 0.03).
Conclusion
This analysis of real-world data suggests that Black race and lower SES are associated with decreased CDK4/6i use. However, among patients treated with CDK4/6i, subsequent toxicity outcomes are similar. Efforts to ensure access to these life-prolonging medications are warranted.
To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario CCO) adjuvant bone-modifying agents in breast cancer guideline.
An Expert Panel ...conducted a systematic review to identify new, potentially practice-changing data.
Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations.
Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer.Additional information can be found at www.asco.org/breast-cancer-guideline.
Purpose
Novel agents such as PI3K and mTOR inhibitors (PI3K/mTORi) have expanded treatment options in metastatic breast cancer (MBC). Nevertheless, mortality rates remain disproportionately high for ...Black patients and patients with lower socioeconomic status. Furthermore, clinical trials for these novel agents lacked diversity, so their toxicity profile in minority populations is uncertain.
Methods
We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database for patients with HR+, HER2− MBC. Multivariable logistic regression was used to evaluate factors associated with PI3K/mTORi use and toxicity outcomes.
Results
A total of 9169 patients with MBC were included in our analysis, of which 1780 (19.4%) received a PI3K/mTORi. We estimated the conditional total effect of insurance through Medicaid, and found lower odds of use of PI3K/mTORi among patients on Medicaid compared to those with commercial insurance (OR 0.73, 95% CI 0.54–0.99, p = 0.049). Odds of PI3K/mTORi use were higher for patients treated at an academic center (OR 1.28, CI 1.06–1.55, p = 0.01). Modeled as a controlled direct effect, Black/African American (Black/AA) race had no impact on odds of PI3K/mTOR use. Black/AA patients had twice the odds of developing hyperglycemia on PI3K/mTORi compared to White patients (OR 2.02, CI 1.24–3.39, p < 0.01).
Conclusion
This analysis of real-world data suggests that the use of PI3K/mTORi is influenced by socioeconomic factors. We also found racial disparities in toxicity outcomes, with Black/AA patients having twice the risk of hyperglycemia. Our findings call for greater efforts to ensure access to novel treatments and improve their tolerability in diverse populations.
Epidermal growth factor receptor (EGFR) is frequently overexpressed in metastatic triple-negative breast cancer (mTNBC). One strategy for overcoming resistance to EGFR inhibition is concomitant ...inhibition of downstream signaling. The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. We evaluated the combination of erlotinib and metformin in a phase 1 study of patients with mTNBC.
Patients with mTNBC who had received at least one prior line of therapy for metastatic disease were eligible. Erlotinib dose was fixed at 150 mg daily. Metformin dose escalation was planned according to a 3 + 3 design. Dose-limiting toxicities (DLT) were assessed during the first 5 weeks of therapy. The primary objective was to determine the maximum tolerated dose of metformin with fixed-dose erlotinib. Secondary endpoints were response rate, stable disease rate, and progression-free survival.
Eight patients were enrolled. The median number of prior therapies for metastatic disease was 2.5 (range, 1-6). No DLT events were reported during the DLT assessment period. Most adverse events were grade 1/2. Grade 3 diarrhea despite maximum supportive care required dose reduction of metformin in one patient. Grade 3 rash led to study withdrawal in one patient. No grade 4 adverse events were reported. The best observed response was stable disease in 2 patients (25%). Median progression-free survival was 60 days (range, 36-61 days).
Erlotinib and metformin were well tolerated in a population of pretreated mTNBC patients but did not demonstrate efficacy in this population.
Background
Adolescents and young adults (AYA) with sarcoma experience both acute and chronic pain related to their disease and treatment. Studies in older adults have reported a high risk of ...persistent opioid use after cancer therapy among previously opioid‐naive patients; however, few studies have evaluated posttreatment opioid use among AYAs. This article describes patterns of new persistent opioid use among AYAs in the year after treatment for sarcoma.
Methods
Opioid‐naive patients who were 10 to 26 years old and diagnosed with sarcoma (2008‐2016) were identified with the IBM Marketscan Database. Included subjects had an International Classification of Diseases code for sarcoma (ninth or tenth revision), received anticancer therapy (chemotherapy, surgery, and/or radiation) within 30 days of the first diagnosis code, and had continuous insurance coverage (commercial or Medicaid) for more than 12 months both before the diagnosis and after the last therapy. The primary outcome was new persistent opioid use, which was defined as at least 2 opioid prescriptions in the 12 months following treatment completion. Covariates included age, sex, insurance, tumor type, surgical procedure, mental health (MH) or substance use diagnoses before or during therapy, and concomitant lorazepam use.
Results
In total, 938 patients met the inclusion criteria; 521 (56%) were male, and 578 (62%) were younger than 18 years. In total, 727 (78%) had commercial insurance, and 273 (29%) had an MH diagnosis either before or during the treatment period. Of the total group, 464 (49%) used opioids during treatment only. Of those who used opioids during treatment, 135 (23%) received at least 2 prescriptions in the year after therapy. In a multivariable analysis, Medicaid versus commercial insurance (odds ratio OR, 1.74; 95% confidence interval CI, 1.15‐2.64) and non–soft tissue sarcoma (OR for Ewing sarcoma, 3.23; 95% CI, 1.81‐5.78; OR for osteosarcoma, 2.05; 95% CI, 1.36‐3.09) conferred a higher likelihood of new persistent use.
Conclusions
In this cohort of AYAs treated for sarcoma, 64% of the patients received opioid prescriptions during treatment, and 23% of these patients became new persistent users. Because of the risks associated with persistent opioid use, studies of novel pain management strategies along with age‐appropriate education and anticipatory guidance are urgently needed.
Lay Summary
Using an insurance claims database, we conducted a study to determine the rate of new persistent opioid use among adolescents and young adults treated for sarcoma.
We found that 64% of adolescents and young adults treated for sarcoma received opioid prescriptions during treatment, and 23% of these patients met the criteria for new persistent opioid use.
These findings support the need for age‐appropriate education and novel pain management strategies in this vulnerable population.
In this cohort of adolescents and young adults treated for sarcoma, 64% of the patients received opioid prescriptions during treatment, and 23% of these patients became new persistent users. Because of the risks associated with persistent opioid use, studies of novel pain management strategies along with age‐appropriate education and anticipatory guidance are urgently needed.
Purpose
Elderly women diagnosed with metastatic breast cancer (MBC) are living longer, however their primary care management may be sub-optimal. Influenza results in preventable hospitalizations and ...deaths. Guidelines recommend the influenza vaccine for those > 65 years and those with cancer but use is unknown.
Methods
A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked data. Patients were included if they were diagnosed with MBC from 1/1/2008–12/31/2017 and were ≥ 65 years of age. The primary outcome was influenza vaccine use among patients surviving
≥
3-years. We conducted multivariable analyses using demographic and clinical factors to identify associations with vaccine use. We compared utilization to cancer-free controls.
Results
We identified 1,970 patients with MBC that survived for
≥
3 years. The median age at diagnosis was 73 years. Furthermore, 1,742 (88%) patients were White, and 153 (8%) patients were Black. Only 1,264 (64%) received an influenza vaccine at least one time and 51% received the vaccine at least two times. A multivariable model found lower odds of vaccine receipt for Black patients (OR = 0.48; 95% CI 0.34–0.68, p < 0.001) and higher odds for patients that saw primary care in the year prior to diagnosis (OR = 1.91, 95% CI 1.57–2.33, p < 0.001). Patients with MBC had lower odds of vaccine use compared to cancer free controls (OR = 0.85, 95% CI 0.74–0.97, p < 0.001).
Conclusion
Over 1/3 of long-term MBC survivors in our cohort did not receive the influenza vaccine. Black patients are about half as likely to be vaccinated. Given the known benefit of the vaccine, improving uptake could be an important strategy to improve outcomes.
The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral ...non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR).
In this retrospective evaluation of 105 patients with stage II-III breast cancer, oxy-hemoglobin (ctO
Hb) from the contralateral non-tumor-bearing breast was collected and analyzed at different time points during NAC. The earliest monitoring imaging time point was after 2-3 weeks receiving taxane. Longitudinal data were analyzed using linear mixed-effects modeling to evaluate the contralateral breast ctO
Hb changes across chemotherapy when corrected for pCR status, age, and BMI.
Patients who achieved pCR to NAC had an overall decrease of 3.88 μM for ctO
Hb (95% CI, 1.39 to 6.37 μM), p = .004, after 2-3 weeks. On the other hand, non-pCR subjects had a non-significant mean reduction of 0.14 μM (95% CI, - 1.30 to 1.58 μM), p > .05. Mixed-effect model results indicated a statistically significant negative relationship of ctO
Hb levels with BMI and age.
This study demonstrates that the contralateral normal breast tissue assessed by DOTBIS is modifiable after NAC, with changes associated with pCR after only 2-3 weeks of chemotherapy.
Sedative-hypnotic medications are used to treat chemotherapy-related nausea, anxiety, and insomnia. However, prolonged sedative-hypnotic use can lead to dependence, misuse, and increased health-care ...use. We aimed to estimate the rates at which patients who receive adjuvant chemotherapy for breast cancer become new persistent users of sedative-hypnotic medications, specifically benzodiazepines and nonbenzodiazepine sedative-hypnotics (Z-drugs).
Using the MarketScan health-care claims database, we identified sedative-hypnotic-naïve patients who received adjuvant chemotherapy for breast cancer. Patients who filled 1 and more prescriptions during chemotherapy and 2 and more prescriptions up to 1 year after chemotherapy were classified as new persistent users. Univariate and multivariable logistic regression analyses were used to estimate odds of new persistent use and associated characteristics.
We identified 22 039 benzodiazepine-naïve patients and 23 816 Z-drug-naïve patients who received adjuvant chemotherapy from 2008 to 2017. Among benzodiazepine-naïve patients, 6159 (27.9%) filled 1 and more benzodiazepine prescriptions during chemotherapy, and 963 of those (15.6%) went on to become new persistent users. Among Z-drug-naïve patients, 1769 (7.4%) filled 1 and more prescriptions during chemotherapy, and 483 (27.3%) became new persistent users. In both groups, shorter durations of chemotherapy and receipt of opioid prescriptions were associated with new persistent use. Medicaid insurance was associated with new persistent benzodiazepine use (odds ratio = 1.88, 95% confidence interval = 1.43 to 2.47) compared with commercial or Medicare insurance.
Patients who receive sedative-hypnotic medications during adjuvant chemotherapy for breast cancer are at risk of becoming new persistent users of these medications after chemotherapy. Providers should ensure appropriate sedative-hypnotic use through tapering dosages and encouraging nonpharmacologic strategies when appropriate.
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