A Review of Fam-Trastuzumab Deruxtecan-nxki in HER2-Positive Breast Cancer.

OBJECTIVE: To review the pharmacology, efficacy, and safety of antibody-drug conjugate fam-trastuzumab deruxtecan-nxki in the treatment of advanced, unresectable, or metastatic breast cancer. DATA SOURCES: Relevant information was identified through a MEDLINE/PubMed (January 2015 to December 2020) literature search. The new drug application, prescribing information, clinical practice guideline, and abstracts from scientific meetings were also reviewed. STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to human studies published in the English language. All studies evaluating the pharmacology, efficacy, or safety of fam-trastuzumab deruxtecan-nxki for breast cancer were included. DATA SYNTHESIS: Fam-trastuzumab deruxtecan-nxki is composed of an anti-human epidermal growth factor receptor 2 (HER2) antibody and topoisomerase I inhibitor (DXd), which causes DNA damage and apoptotic cell death. Major phase I and phase II clinical trials established the efficacy and safety of fam-trastuzumab deruxtecan-nxki for treatment of HER2-positive advanced, unresectable, or metastatic breast cancers that are refractory or intolerant to standard treatment. In these trials, the response rate was 60.9% (95% CI = 53.4-68.0) Common adverse effects included fatigue, nausea, vomiting, decreased appetite, constipation, diarrhea, alopecia, neutropenia, anemia, and thrombocytopenia. Serious adverse effects included interstitial lung disease or pneumonia, febrile neutropenia, left ventricular dysfunction, and embryo-fetal toxicity. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Fam-trastuzumab deruxtecan-nxki is an option for HER2-positive breast cancer following 2 previous lines of HER2-targeted therapy. CONCLUSIONS: Fam-trastuzumab deruxtecan-nxki is an effective treatment for HER2-positive breast cancer in the metastatic setting, but randomized controlled trials are needed.

CDK 4/6 inhibitors are associated with a high incidence of thrombotic events in women with breast cancer in real-world practice.

PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors are integral treatment for advanced hormone receptor positive breast cancer; however, venous thromboembolic events (VTE) occurred in 1%-5% of clinical trial patients. Thrombosis rates in the real-world setting remain unclear. We aimed to define the rate of thromboembolic events, risk factors for thrombosis on CDK 4/6 inhibitors and evaluate the Khorana VTE risk score as a predictive tool for VTE in patients on CDK 4/6 therapy. METHODS: Multicenter retrospective analysis of adult breast cancer patients prescribed palbociclib, ribociclib, or abemaciclib. The primary endpoint was thrombosis during treatment or within 30 days of CDK inhibitor discontinuation. Cox regression was used to model time-to-thrombosis, starting from a patient's initiation of CDK 4/6 therapy. The extended Kaplan-Meier method and Cox modeling were used to assess the effect of time-varying thrombosis status on overall survival. RESULTS: Two hundred and sixty-six patients were included (89% on palbociclib, 14% on abemaciclib, 7% on ribociclib). Twenty-nine thrombotic events occurred in 26 (9.8%) women. Of these events, 72% were venous and 34% were arterial. The 1-year incidence of thrombosis was 10.4% overall, 10.9% on palbociclib, 8.3% on ribociclib, and 4.8% on abemaciclib. Hemoglobin less than 10 g/dL was a statistically significant predictor of thrombosis (HR 3.53, P: .014). Khorana score ranged from 0-3, with the majority between 0 and 1 and was not predictive of VTE. Thrombosis was associated with reduced overall survival (HR 1.28, P: .128, median 7.3 months) compared to not having a CDK-associated clot (median 35.7 months). DISCUSSION: VTE in our analysis is higher than reported in clinical trials and arterial thrombosis comprised over one-third of events. The highest incidence was with palbociclib, followed by ribociclib. Khorana score did not predict VTE risk. Larger, real-world studies are needed. The role for prophylactic anticoagulation is yet to be defined in this patient population.

Trends in the delivery of care to oncology patients in the United States: Emphasis on the role pharmacists on the healthcare team.

OBJECTIVE: The purpose of this study was to identify trends in oncology care that allow one to forecast workforce supply and demand, the training and skills needed by the oncology pharmacist for the likely future of oncology care. METHODS: Interviews were conducted with experienced oncology pharmacists in leadership roles at 20 organizations balanced by geographic region and type of practice site (academic or community/ambulatory). Results were analyzed using descriptive statistics and theme identification. RESULTS: Practice sites differed widely in numbers of patient visits, practitioner/patient ratios, residency program presence, and other structural features. Despite this, the majority reported an expectation of growth in cancer patients, oncology physicians, oncology pharmacists, pharmacy technicians, oncology nurses, and advanced practice practitioners in the next two to five years. Fifty percent of sites currently support Post Graduate Year 2 (PGY2) oncology residencies. At least 50% reported routine pharmacist involvement in 12 clinical functions. More future involvement was predicted for immunotherapy (80%) and oral oncolytic therapy (90%). Interprofessional involvement was reported for a broad variety of practice-related committees and patient education teams. Limited pharmacist involvement in credentialing, quality measurement, and value-based reimbursement systems was found. CONCLUSION: Anticipated increases in demand for oncology pharmacists strongly suggest the need for more PGY2 oncology residency programs and on-the-job oncology training programs. Oncology pharmacists are currently involved in many clinical and administrative functions including multidisciplinary management. While a core set of clinical functions has been identified, oncology pharmacists must prepare for the increased use of oral oncology agents and immunotherapy. Pharmacist involvement in value-based reimbursement and other data-based quality outcome measurements should be increased to optimize involvement in team-based patient care.

Off-label versus on-label prescribing of oral oncology agents on time to receipt of medication in patients with soft tissue sarcoma.

PURPOSE: Off-label prescribing of oral oncology agents has been explored in the treatment of soft tissue sarcoma. The time for a prior authorization approval or rejection for an off-label use can be lengthy. The purpose of this study is to capture this burden by comparing the time it takes for patients to receive off-label versus on-label treatment for their soft tissue sarcoma. PATIENTS AND METHODS: In this retrospective chart review study, patients aged 18 and older who received a new prescription for an oral oncology agent for soft tissue sarcoma from one of three sarcoma providers at Oregon Health & Science University oncology clinics between March 2014 and February 2016 were included. Objectives included comparing the effect of off-label to on-label prescribing of oral oncology agents on time to receipt of medication and patient copays for a 30-day supply of oral chemotherapy agent(s). RESULTS: The time to receipt of medication (median (IQR)) for the off-label group (N = 26) was 12.5 (3.3 to 30.8) days compared to the on-label group (N = 29), which was 8.0 (4.0 to 15.0) days (p = 0.327). The patient cost was $0.00 ($0.00 to $20.00) for the off-label group (N = 18) compared to $3.00 ($0.00 to $68.80) for the on-label group (N = 18) (p = 0.467). CONCLUSIONS: There were no differences in the time to receipt of medication or patient cost between off-label and on-label prescriptions in soft tissue sarcoma patients. Despite lack of statistical significance, these results are meaningful to patient care and require further study to investigate these findings.

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer.

OBJECTIVE: To review the pharmacology, efficacy, and safety of the cyclin-dependent kinase (CDK) inhibitor, abemaciclib, in the treatment of advanced or metastatic breast cancer (MBC). DATA SOURCES: Relevant information was identified through a MEDLINE/PubMed (January 2000 to June 2018) literature search. The new drug application, prescribing information, and abstracts and posters from scientific meetings were also reviewed. STUDY SELECTION/DATA EXTRACTION: The literature search was limited to human studies published in the English language. Phase 1, 2, and 3 studies evaluating the pharmacology, efficacy, or safety of abemaciclib for breast cancer were included. DATA SYNTHESIS: Abemaciclib is an oral, potent, small molecule inhibitor of CDK4 and CDK6 activity, which blocks retinoblastoma tumor suppressor protein phosphorylation and thereby prevents progression through the cell cycle. Three major clinical trials, MONARCH 1, 2, and 3, established the efficacy and safety of abemaciclib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or MBC. In these trials, response rates were promising, ranging from 19.7% to 59%, and median progression-free survival was significantly prolonged over the control arm in 2 of the trials. Common adverse effects included diarrhea, neutropenia, nausea, abdominal pain, infections, and fatigue. Relevance to Patient Care and Clinical Practice: Although no head-to-head studies have been completed between the CDK4/6 inhibitors, abemaciclib may be an attractive option because of its continuous dosing and ability to be used as monotherapy. CONCLUSIONS: Abemaciclib is an effective and well-tolerated treatment for HR-positive, HER2-negative advanced or metastatic breast cancer.

Phase II open label pilot trial of aprepitant and palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic FOLFOX chemotherapy for the treatment of colorectal cancer.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) causes significant morbidity among colorectal cancer patients, receiving fluorouracil, oxaliplatin, and leucovorin (FOLFOX) chemotherapy even with standard antiemetic prophylaxis. The purpose of this study is to determine if the addition of aprepitant to standard antiemetic therapy improves CINV in these patients. METHODS: Patients receiving FOLFOX for colorectal cancer were given antiemetic prophylaxis with aprepitant 125 mg orally on day 1 and 80 mg on days 2 and 3. Palonosetron 0.25 mg was given IV push on day 1 only. Dexamethasone 12 mg was administered orally on day 1 and 8 mg each morning on days 2 through 4. Assessments including emetic events, rescue doses, nutritional intake, and appetite were recorded in a patient diary which was returned to study personnel in the following cycle. RESULTS: Of the 53 patients screened, 50 were evaluable and had a complete dataset for cycle 1. For the first cycle, 74% of patients achieved a complete response (CR), 22% achieved a major response and 4% experienced treatment failure. The percentage of patients achieving a CR remained high throughout each cycle at 83, 83, and 86% for cycles 2, 3, and 4, respectively. Appetite and nutritional status remained largely unchanged throughout treatment. Adverse events occurring in more than 10% of patients included diarrhea (13.6%), fatigue (12.6%), and neutropenia (11%). CONCLUSIONS: Aprepitant added to standard antiemetic therapy appears to be an effective and safe regimen for prevention of CINV in patients receiving FOLFOX.

Pelvic venous insufficiency: imaging diagnosis, treatment approaches, and therapeutic issues.

OBJECTIVE. The purposes of this article are to review the causes of pelvic congestion syndrome and the imaging used to make the diagnosis and to summarize the treatment options. CONCLUSION. Pelvic congestion syndrome is one of many causes of chronic pelvic pain. It is thought to arise from ovarian and pelvic venous incompetence. Findings from various noninvasive imaging studies, such as Doppler ultrasound and MRI, in association with the clinical symptoms are critical in establishing the diagnosis.