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.

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.

Physician home visits by palliative medicine fellow.

BACKGROUND: Physician home visits (HVs) are an important model of care for the terminally ill. Hospice and palliative medicine (HPM) fellows make a minimum of 25 HVs. OBJECTIVE: To describe HPM fellow hospice HVs in an academic palliative medicine practice. METHODS: Retrospective chart review of HVs conducted by 1 HPM fellow. RESULTS: Twenty-five HVs were made to 21 hospice patients. Nineteen had advanced cancer. Indications for visits were symptom management (22) and education (21). On average 2.8 symptoms (± SD 1) were addressed on each visit, usually pain. Medications were reviewed at every visit. CONCLUSIONS: HVs are an important part for patient care and fellow education, which provided an opportunity for medication revision and symptom education.

Modern management of malignant hypercalcemia.

Hypercalcemia occurs in 10% to 20% of those with advanced cancer. It is considered an oncologic emergency. Presenting symptoms include common gastrointestinal symptoms that may be difficult to differentiate from tumor or treatment-related symptoms. These include nausea, vomiting, and constipation. As levels increase or if development is rapid, neuropsychiatric symptoms such as delirium can develop. Untreated it will lead to coma and death. Current preferred therapies are the bisphosphonate agents, zoledronate and pamidronate with saline rehydration.

The business of palliative medicine--part 6: clinical operations in a comprehensive integrated program.

The medical care of individuals with advanced disease is complex and has historically been fragmented and suboptimal. Palliative medicine attempts to address these needs. The Harry R. Horvitz Center for Palliative Medicine at the Cleveland Clinic is an established comprehensive integrated program. Structured and seamless clinical operations are important to ensure the best delivery of high-quality medical care and continuity for those affected by life-limiting illness.

Comfort measures: practical care of the dying cancer patient.

Most patients with advanced malignancy will die of their disease. Care of the dying is therefore a fundamental skill for the oncologist. Although protocols exist in other countries, there is no established protocol in the United States. We present a protocol for management of the dying that is clinically useful and review the existing evidence-base.

Scopolamine for cancer-related nausea and vomiting.

Nausea and vomiting is a common and troublesome symptom in advanced cancer. There have been different approaches described for the management of nausea and vomiting, specifically empirical and etiological. Scopolamine is listed in textbooks as a useful medication in management of nausea and vomiting in this setting, although there is no published data to support this recommendation. We present three cases that support the use of scopolamine in an etiologically based approach for management of nausea in advanced cancer.

Errors in opioid prescribing: a prospective survey in cancer pain.

CONTEXT: Cancer pain is debilitating and has multidimensional consequences. It can be treated adequately in up to 90% of patients by following pain management guidelines. Nevertheless, inadequate pain control remains a global problem. OBJECTIVES: We surveyed prescribing patterns in patients referred to our Palliative Medicine Program (PMP) to identify common errors in opioid use. METHODS: Consecutive cancer patients seen by our PMP were prospectively surveyed for the presence of pain and errors in opioid prescribing at the time of initial consultation. Our recommendations to correct and optimize pain management also were recorded. RESULTS: One hundred eighty-six consecutive cancer patients were screened. One hundred seventeen (63%) had cancer pain, 151 opioid prescribing errors were detected, and 147 different recommendations were made. Most common were failure to order around-the-clock opioids for constant pain, and the failure to treat or prevent opioid side effects. Multiple errors were more common in females, but the sex difference did not reach statistical significance. There was no difference in the errors by pain severity or reason for consultation. CONCLUSION: Opioid prescribing errors were common. Females may be at greater risk of multiple errors. A PM consultation program is effective in identifying and correcting a wide variety of opioid prescribing errors.

A comparative study of 2 sustained-release morphine preparations for pain in advanced cancer.

PURPOSE: Several sustained-release morphine (SRM) formulations are available internationally. This study compared 2 such products available in the United States, SR1 and SR2. PATIENTS AND METHODS: In an open-label study, patients with advanced cancer pain were randomized to receive SR1 or SR2 every 12 hours around-the-clock (ATC) for 5 days, with immediate release (IR) liquid morphine for rescue dosing (RD). Efficacy, safety, and patient acceptability were determined. RESULTS: A total of 32 patients were evaluable for efficacy and toxicity. Pain scores, RD dosage, RD frequency over 5 days, RD within 3 hours before and after the scheduled SRM, and 8 of the 11 evaluated side effects were higher in the SR1 group. At presumed morphine steady state (day 3), pain scores (P = .05), RD dosage (P = .07), RD frequency (P = .07), and number of RD +/-3 hours from scheduled SRM dose (P = .05) were consistently greater in the SR1 group (despite a higher median morphine dose in that group). There was a clinically important and directionally consistent trend that favored SR2, although not all were statistically significant. Patient preference favored SR2 (P < .05). Neither group had difficulty swallowing SR1 or SR2. CONCLUSIONS: This is the first study that directly compared two 12-hour SRM formulations. The data suggested, by multiple clinically important measures, that SR2 may provide superior analgesic efficacy and less toxicity compared to SR1. It also supports the concept that it cannot be assumed that different SR formulations of a given opioid are clinically equivalent. A larger study is needed to confirm our findings.

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.

Respiratory function during parenteral opioid titration for cancer pain.

BACKGROUND: Respiratory depression is the most feared opioid-related side-effect yet research on the topic is sparse. We evaluated changes in respiratory parameters during parenteral opioid titration for cancer pain to determine if opioid titration was associated with evidence of hypoventilation. The primary outcome measure was to measure changes in end-tidal CO(2) (ET-CO(2)) during opioid titration to pain control. METHODS: Subjects with severe cancer pain admitted for parenteral opioid titration for poorly controlled pain were eligible. Those who were oxygen dependent were excluded. ET-CO(2), O(2) saturation, respiratory rate (RR), and vital signs were monitored daily until pain control was achieved. RESULTS: 30 patients completed the study of which 29 are reported. The mean ET-CO(2) at initial evaluation was 33.39 -/+ 5.0 and 34.79 -/+ 5.7 mmHg at pain control (P =0.14, 95% CI -0.5 to 3.3). None had an ET-CO(2) > or =50 mmHg. All maintained O(2) saturation > or = 92%. RR dropped transiently below 10/minute in two subjects. CONCLUSIONS: Parenteral opioid titration for relief of cancer pain was not associated with respiratory depression as demonstrated by significant changes in ET-CO(2) or oxygen saturation in non-oxygen dependent cancer patients.

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.

Cancer symptom assessment instruments: a systematic review.

PURPOSE: A variety of assessment instruments have been created to identify cancer symptoms. We reviewed systematically cancer symptom assessment instruments published in English. METHODS: A systematic search of the MEDLINE database, Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and EMBASE was performed. Non-peer-reviewed articles were identified through BIOSIS. Articles were accessed through the related article links in PubMed and references were searched by hand. Studies were included if the instrument had symptom assessment as the primary outcome. Quality-of-life instruments were excluded. RESULTS: We identified 21 instruments; some had undergone modification or validation. An additional 28 studies examined symptom prevalence and interrelations; many involved symptom checklists. Studies varied in design, patient characteristics, symptoms, and outcome. Meta-analysis was not possible due to heterogeneity in design, study outcomes, and validation. Seventy-six articles and two conference abstracts (derived from MEDLINE, Cochrane, CINAHL, EMBASE, BIOSIS, related articles link in PubMed, and search by hand) met inclusion/exclusion criteria. The electronic search (without related links) yielded only 26% of those articles and conference abstracts that met inclusion criteria. Searches by hand of related articles identified 59% of studies. CONCLUSION: Twenty-one instruments were identified as appropriate for clinical use. The instruments vary in symptom content and extent of psychometric validation. Both comprehensive and shorter instruments have been developed, and some instruments are intended for specific symptom assessment or symptoms related to treatment. There is no ideal instrument, and the wide variety of instruments reflects the different settings for symptom assessment. Additional research is necessary.