Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors.

PURPOSE: Everolimus with exemestane (EVE+EXE) was FDA-approved to treat metastatic hormone receptor-positive breast cancer (mHRBC) based on BOLERO-2. However, none of those patients received prior CDK4/6 inhibitors. The purpose of this study is to evaluate the efficacy of EVE+EXE in mHRBC after CDK4/6 inhibitors. METHODS: A retrospective review of patients ≥18 years old with mHRBC treated with EVE+EXE, for ≥30 days, at our institution from January 1, 2012, to April 1, 2020 was conducted. Primary objective was to compare progression free survival (PFS) for EVE+EXE between patients with and without prior exposure to CDK4/6 inhibitors. Secondary outcomes included overall survival and safety. RESULTS: 192 patients were included in the study (n = 79, prior CDK4/6 inhibitor use; n = 113, no prior CDK4/6 inhibitor use). Baseline patient characteristics were similar between groups. Greater number of prior therapies before EVE+EXE use increased risk of disease progression (P = .017). Patients with prior CDK4/6 inhibitor use had a lower median PFS of 3.8 months (95% CI: 3.4-4.7) vs. 5.4 months (95% CI: 3.9-6.2) for patients without prior CDK4/6 inhibitor use, with a HR for progression of 1.46 (95% CI: 1.08 to 1.97, P = .013). Overall survival between groups was not significantly different. CONCLUSION: Patients who received a prior CDK4/6 inhibitor had a lower median PFS benefit from EVE+EXE compared to those who did not, without differences in overall survival. Although PFS is expected to decrease with subsequent lines of therapy, it is reasonable to use EVE+EXE after CDK4/6 inhibitors in selected patients, recognizing that additional benefit is modest.

Narrative review: furosemide for hypercalcemia: an unproven yet common practice.

Although primary hyperparathyroidism is the most common cause of hypercalcemia, cancer is the most common cause requiring inpatient intervention. An estimated 10% to 20% of all patients with cancer have hypercalcemia at some point in their disease trajectory, particularly in advanced disease. Aggressive saline hydration and varying doses of furosemide continue to be the standard of care for emergency management. However, a review of the evidence for the use of furosemide in the medical management of hypercalcemia yields only case reports published before the introduction of bisphosphonates, in contrast to multiple randomized, controlled trials supporting the use of bisphosphonates. The use of furosemide in the management of hypercalcemia should no longer be recommended.

A day in the life: a case series of acute care palliative medicine--the Cleveland model.

Palliative care in advanced disease is complex. Knowledge and experience of symptom control and management of multiple complications are essential. An interdisciplinary team is also required to meet the medical and psychosocial needs in life-limiting illness. Acute care palliative medicine is a new concept in the spectrum of palliative care services. Acute care palliative medicine, integrated into a tertiary academic medical center, provides expert medical management and specialized care as part of the spectrum of acute medical care services to this challenging patient population. The authors describe a case series to provide a snapshot of a typical day in an acute care inpatient palliative medicine unit. The cases illustrate the sophisticated medical care involved for each individual and the important skill sets of the palliative medicine specialist required to provide high-quality acute medical care for the very ill.

The business of palliative medicine - part 5: service utilization in a comprehensive integrated program.

The aim of palliative medicine is to provide multidisciplinary comprehensive care in advanced illness. Patient and family utilization of various product service lines offered by the Harry R Horvitz Center for Palliative Medicine at the Cleveland Clinic Foundation was studied. Newly referred patients were followed up prospectively until 85% had either died or been lost to follow-up. Demographic, clinical, and referral data were recorded; subsequent product service line utilization was updated daily. The total study period was 171 days, and 238 patients entered. Acute care inpatient unit, outpatient clinic visits, and 24-hour phone contacts were the most frequently used product service lines. Patients had a median of 3 contacts (range, 1 to 27) with individual service lines. Multiple palliative medicine product service lines were utilized often, with repeated use of the individual service lines. A comprehensive integrated palliative medicine program is necessary to fully meet the complex needs of those with advanced disease.

Deaths in an academic medical center.

The number of inpatient deaths in a calendar year in an academic medical center was reviewed from a computerized database. The total number was 1222. The median length of hospital stay for those who died was 7 days (range, 1-190); 404 (33%) were 75 years or older. There were 678 (55%) males and 544 (45%) females. The pulmonary medicine service had the most deaths with 290 (24%) followed by hematology/oncology 230 (18%). The most common primary diagnoses in the decedents were subendocardial infarction 58 (5%), congestive heart failure 57 (5%), and pneumonia 45 (4%). The most common diagnostic-related groups (DRGs) were respiratory system disorders (475), 98 (8%); tracheostomy (483), 75 (6%); and heart surgery (110), 65 (5%). Frequent procedures done prior to death were mechanical ventilation (<96 hours) 101 (8%), and mechanical ventilation (>96 hours) 55 (5%), and tracheostomy 54 (4%). Invasive procedures were common. Forty-five percent of the predeath patient days were spent in intensive care units. Palliative medicine was involved in the care of 20% of all the decedents.

'I'm not that sick!' Overcoming the barriers to hospice discussions.

Hospice programs care for patients facing life-limiting illness. Although patients and family members report that they are satisfied once they are enrolled in a hospice service, many patients are referred late or not at all. Several barriers and misconceptions about hospice likely contribute to its underuse. We explore these issues and provide guidance to more effectively communicate with patients about hospice services.

Appetite and cancer-associated anorexia: a review.

Appetite is governed by peripheral hormones and central neurotransmitters that act on the arcuate nucleus of the hypothalamus and nucleus tactus solitarius of the brainstem. Cancer anorexia appears to be the result of an imbalance between neuropeptide-Y and pro-opiomelanocortin signals favoring pro-opiomelanocortin. Many of the appetite stimulants redress this imbalance. Most of our understanding of appetite neurophysiology and tumor-associated anorexia is derived from animals and has not been verified in humans. There have been few clinical trials and very little translational research on anorexia despite its prevalence in cancer.

Opioid rotation in cancer patients: pros and cons.

Opioid rotation involves changing from one opioid to another using correct equianalgesic conversion techniques to achieve better analgesia and/or fewer side effects. The strategy appears to work because of significant interindividual variations in response to both analgesic activity and toxicity. Although there are many retrospective studies, few prospective controlled trials of opioid rotation have been published. The practical and theoretical advantages of opioid rotation include improved analgesia, reduced side effects, cost reduction, and improved compliance. Disadvantages include problems related to inaccurate conversion tables, limited availability of certain opioid formulations, drug interactions, and the possibility of increased expense. Weighing the advantages and disadvantages is essential prior to making a decision about opioid rotation selection.

Common symptoms in advanced cancer.

The key points of this article are anorexia and cachexia are: A major cause of cancer deaths. Several drugs are available to treat anorexia and cachexia. Dyspnea in cancer usually is caused by several factors. Treatment consists of reversing underlying causes, empiric bronchodilators, cortico-steroids--and in the terminally ill patients-opioids, benzodiazepines,and chlorpromazine. Delirium is associated with advanced cancer. Empiric treatment with neuroleptics while evaluating for reversible causes is a reasonable approach to management. Nausea and vomiting are caused by extra-abdominal factors (drugs,electrolyte abnormalities, central nervous system metastases) or intra-abdominal factors (gastroparesis, ileus, gastric outlet obstruction, bowel obstruction). The pattern of nausea and vomiting differs depending upon whether the cause is extra- or intra-abdominal. Reversible causes should be sought and empiric metoclopramide or haloperidol should be initiated. Fatigue may be caused by anemia, depression, endocrine abnormalities,or electrolyte disturbances that should be treated before using empiric methylphenidate. Constipation should be treated with laxatives and stool softeners. Both should start with the first opioid dose.

The financial benefits of acute inpatient palliative medicine: an inter-institutional comparative analysis by all patient refined-diagnosis related group and case mix index.

Financial comparisons of acute care hospital services are possible using the Centers for Medicare & Medicaid Services case mix index (CMI) and All Patient Refined-Diagnosis Related Group (APR-DRG) data. We compared The Cleveland Clinic's Inpatient Palliative Medicine (CCIPM) acute care unit's CMI and APR-DRG data with national and peer institution data. Total mean charges per admission to the CCIPM unit were 7,800 dollars lower than at other peer institutions despite an equivalent severity of illness and longer length of stay and higher mortality in the CCIPM unit. The lower charges were due primarily to lower laboratory and pharmaceutical charges. We conclude that an acute inpatient palliative medicine unit operating within a comprehensive integrated palliative medicine program is cost-effective in providing specialized care for people with advanced disease.

Opioids in cancer pain: common dosing errors.

Many individuals with advanced malignancy continue to suffer from pain and, consequently, impaired quality of life. The clinical scenarios in advanced cancer pain are complex, and successful management may require a more sophisticated and individualized approach than suggested by the World Health Organization guidelines. In patients referred to the Harry R. Horvitz Center for Palliative Medicine in Cleveland, numerous commonly occurring errors in opioid use have been noted. This article describes these errors and offers strategies with which to improve outcomes for patients suffering with cancer pain.

Initial voluntary program standards for fellowship training in palliative medicine.

Initial voluntary standards for fellowship programs in palliative medicine were developed through a collaborative process involving the directors of fellowship training programs, the American Academy of Hospice and Palliative Medicine (AAHPM), and the American Board of Hospice and Palliative Medicine (ABHPM). These groups worked with a consultant and representatives from the American Board of Medical Specialties (ABMS) and the Accreditation Council for Graduate Medical Education (ACGME) to create a training structure for the programs that will maximize the likelihood for recognition and accreditation of the subspecialty. An accreditation group modeled after an ACGME residency review committee will be formed to review and adopt the standards, then accredit programs voluntarily.

A syllabus for fellowship education in palliative medicine.

Recent years have seen significant growth in palliative medicine training programs and positions. There are plans to pursue palliative medicine specialty status with the American Board of Medical Specialties and accreditation of fellowship programs with the American College of Graduate Medical Education. A work group of program directors, supported initially by the Cleveland Clinic and then by the American Board of Hospice and Palliative Medicine, has recently published standards for fellowship training. Despite this, fundamental questions remain about defining the field and delineating the knowledge and skills expected following completion of specialty training. In this article, we describe the first fellowship program in palliative medicine (PMP) in the United States, developed and supported by the Cleveland Clinic Foundation. The program has been implemented as part of the Harry R. Horvitz Center for Palliative Medicine, founded in 1987 as the first comprehensive integrated US program in this field. This training program, in existence since 1989, features a traditional rotational structure with an inpatient primary care service, inpatient consult services, and an outpatient consult/hospice service. This article outlines the syllabus developed for this fellowship, given what we believe to be the essential knowledge base for the field of palliative medicine.

Opioids, respiratory function, and dyspnea.

Dyspnea, the sensation of difficult breathing, is a common debilitating symptom in advanced cancer and chronic progressive cardiopulmonary disease. Primary treatment is correction of the underlying etiology. In incurable illness wherein the cause is irreversible and the goal is palliation, opioids are the drugs of choice for symptomatic relief. This article reviews current knowledge in the pathophysiology of dyspnea, proposed opioid mechanism of action, and evidence of efficacy.

The business of palliative medicine--Part 2: The economics of acute inpatient palliative medicine.

Economic feasibility is a major factor in the viability of established acute inpatient palliative medicine. Several clinical, administrative, and financial parameters determine the financial health of inpatient care. Financial management metrics include case mix index (CMI) (as determined by the Federal Register as an assigned relative weight to the diagnosis-related group (DRG) reflecting resource consumption), direct costs, indirect costs, contribution margin, and in the future of all patient revised-DRG (APR-DRG). Both census and length of stay will have a major impact on these financial metrics. The type of patient referral and clinical decisions will influence direct costs and revenues. In the future, an international CMI or APR-DRG will allow palliative inpatient units to compare disease severity, resource utilization, and outcome measures.

A phase II study of hydrocodone for cough in advanced cancer.

PURPOSE: Cough is a common symptom in advanced cancer. The use of hydrocodone as an antitussive has not been studied previously in this setting. This study evaluates hydrocodone for cough in advanced cancer METHODS: The results presented are from a phase II study with dose titration. SETTING: Palliative medicine program in a tertiary referral center PATIENTS: 25 consecutive patients with cough from irreversible causes, on a stable opioid regimen for the prior 24 hours, and no previous or current use of hydrocodone for cough. INTERVENTION: 5 mg hydrocodone was administered twice daily. The dose was then titrated daily (maximum: 60 mg/24 h), if needed, until a > or = 50 percent improvement of the frequency of cough was achieved and then maintained for three consecutive days. MEASUREMENTS: Cough severity, frequency, complications, and hydrocodone side effects. RESULTS: 20 persons (10 women and 10 men) completed study evaluation. Median age was 63 years (range: 42-82). Nine patients had lung cancer and seven had lung or pleura metastases; 19 patients had at least 50 percent improvement of their cough frequency. The median best response was 70 percent improvement in the cough frequency (range: 50-90 percent). Median hydrocodone dose associated with the best response was 10 mg/day (range: 5-30 mg/day). Cough severity, frequency, associated symptoms and complications, and activities of daily living improved significantly. Side effects of hydrocodone (dry mouth, nausea, and drowsiness) were tolerable and rated as mild. CONCLUSIONS: Hydrocodone is effective and safe to treat cough in advanced cancer A starting dose of 10 mg per day in divided doses seems effective. Dose escalation may be required. Most improved within one day.

Nausea and vomiting in advanced cancer.

Nausea and vomiting are very common symptoms in cancer both treatment and non-treatment related. Many complications of advanced cancer such as gastroparesis, bowel and outlet obstructions, and brain tumors may have nausea and vomiting or either symptom alone. In a non-obstructed situation, nausea may be more difficult to manage and is more objectionable to patients. There is little research on management of these symptoms except the literature on chemotherapy induced nausea where guidelines exist. This article will review the etiologies of nausea and vomiting in advanced cancer and the medications which have been used to treat them. An etiology based protocol to approach the symptom is outlined.

Delirium in palliative medicine: a review.

Delirium is a devastating complication of general medical and surgical populations but of particular importance in palliative medicine. It is a clinical syndrome that is often not recognized and, therefore, not treated appropriately. The presence of delirium is a predictor of increased morbidity and mortality, longer hospitalization, and more likely discharge to a nursing facility. This article reviews the pathophysiology, etiology, diagnosis, and treatment of delirium in the palliative medicine population.

Palliative medicine fellowship: a study of resident choices.

CONTEXT: There are no data on the motives or characteristics of physicians choosing fellowship training in Hospice and Palliative Medicine (HPM). OBJECTIVES: To understand more about the residents who choose HPM and what leads them to this decision. METHODS: An electronic survey of HPM fellows initiating training in July 2009. RESULTS: Seventy-six physicians began the study, with 62 responders (82%) completing all questions. Fifty-five percent were aged 30-40 years, and 61% were female. Sixty-eight percent were non-Hispanic Caucasian, 24% were Asian, and none were African American. Fifty-five percent were trained in internal medicine. Most (86%) asserted that the care of a dying, critically ill, or symptomatic person impacted their decision to enter the field of HPM. Sixty-three percent did not feel prepared to manage dying patients, and 41% felt personal regret about the care they delivered. The major reasons for choosing the specialty were a desire to contribute to relief of suffering (79%), enhance end-of-life care (73%), and improve communication (78%). Ninety-five percent received negative comments about their career choice. Fifty-nine percent had no exposure to hospice or palliative medicine in medical school, whereas 61% had an exposure available during residency. Forty-seven percent decided to enter a fellowship in the third year of residency, and 33% applied after practicing in their primary specialty for a median of 10 years. Accreditation, strength of education, and a hospital palliative medicine service were required by the majority for selection of a fellowship program. CONCLUSION: Negative experiences with end-of-life care in residency, particularly in the intensive care unit, continue to be a factor in selection of HPM as a specialty. Many residents make their decision to enter the field and apply during Postgraduate Year 3. Most received negative comments about the choice. Fellows require a broad range of experience when selecting a fellowship program.