Impact of Proton Pump Inhibitor Use on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Cancer Patients.

BACKGROUND: The gut microbiome plays a critical role in modulating the therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) are commonly used in cancer patients and may affect the gut microbiome by altering gut pH. OBJECTIVE: To evaluate if concurrent use of PPI is associated with overall survival (OS) and progression-free survival (PFS) in patients with stage IV non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma, or head and neck squamous cell carcinoma. METHODS: This was a single-center retrospective cohort study of advanced cancer adult patients who received nivolumab or pembrolizumab between September 1, 2014, and August 31, 2019. Concomitant PPI exposure was defined as PPI use 0 to 30 days before or after initiation of ICIs. Treatment outcome was OS and PFS. RESULTS: A total of 233 patients were included in our study. Concomitant PPI use was not significantly associated with OS (hazard ratio [HR] = 1.22; 95% CI = 0.80-1.86) or PFS (HR = 1.05; 95% CI = 0.76-1.45) in patients with ICI use. The effect estimates were robust after adjusting for covariates in multivariate analysis and in patients with NSCLC. CONCLUSION AND RELEVANCE: Concomitant PPI use was not associated with the effectiveness of nivolumab or pembrolizumab. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as the time window and indication of PPI exposure and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on the effectiveness of ICI use.

Employment Trends for Doctor of Pharmacy Graduates of Research-Intensive Institutions, 2013-2017.

Objective. To determine the current state of employment for doctor of pharmacy (PharmD) graduates based on 5-year trends among graduates of research-intensive institutions and the Pharmacist Demand Index. Methods. Data from a cross-sectional survey of PharmD graduates from 10 research-intensive colleges of pharmacy conducted over a 5-year period were used to generate an overview of graduating students' experiences and the outcomes of their job searches. Results. The average response rate of graduates of programs over the 5 years was 75.4%. Overall, 86% of graduates had postgraduate placements (ie, jobs, residencies, fellowships, further education) at the time of graduation. Across all years, 85% of respondents who had placements indicated they were satisfied with the postgraduation offer they received. Conclusion. An examination of postgraduate outcomes of research-intensive schools and the Pharmacist Demand Indicator over the past 5 years indicates a trend toward a balance between the supply and demand for pharmacists. Careful attention needs to be given to these two metrics moving forward.

Role of Bone-Modifying Agents in Multiple Myeloma: American Society of Clinical Oncology Clinical Practice Guideline Update.

Purpose To update guideline recommendations on the role of bone-modifying agents in multiple myeloma. Methods An update panel conducted a targeted systematic literature review by searching PubMed and the Cochrane Library for randomized controlled trials, systematic reviews, meta-analyses, clinical practice guidelines, and observational studies. Results Thirty-five relevant studies were identified, and updated evidence supports the current recommendations. Recommendations For patients with active symptomatic multiple myeloma that requires systemic therapy with or without evidence of lytic destruction of bone or compression fracture of the spine from osteopenia on plain radiograph(s) or other imaging studies, intravenous administration of pamidronate 90 mg over at least 2 hours or zoledronic acid 4 mg over at least 15 minutes every 3 to 4 weeks is recommended. Denosumab has shown to be noninferior to zoledronic acid for the prevention of skeletal-related events and provides an alternative. Fewer adverse events related to renal toxicity have been noted with denosumab compared with zoledronic acid and may be preferred in this setting. The update panel recommends that clinicians consider reducing the initial pamidronate dose in patients with preexisting renal impairment. Zoledronic acid has not been studied in patients with severe renal impairment and is not recommended in this setting. The update panel suggests that bone-modifying treatment continue for up to 2 years. Less frequent dosing has been evaluated and should be considered in patients with responsive or stable disease. Continuous use is at the discretion of the treating physician and the risk of ongoing skeletal morbidity. Retreatment should be initiated at the time of disease relapse. The update panel discusses measures regarding osteonecrosis of the jaw. Additional information is available at www.asco.org/hematologic-malignancies-guidelines and www.asco.org/guidelineswiki .

StrengthsFinder® signature themes of talent in pharmacy residents at four midwestern pharmacy schools.

BACKGROUND AND PURPOSE: StrengthsFinder® is a widely-used assessment that can be used to help student pharmacists discover their talents (i.e., signature themes [STs]) and develop their leadership skills. The assessment has also been used in pharmacy residents, but the prevalence of various STs in that group has not been compared to those in student pharmacists. EDUCATIONAL ACTIVITY AND SETTING: Residents from four midwestern pharmacy institutions completed StrengthsFinder® 2.0 and received their top five STs. STs were organized and examined by domains (executing, influencing, relationship building, and strategic thinking). StrengthsFinder® data on student pharmacists were obtained from a previously published study. The distribution of the themes and domains was compared between residents and student pharmacists. FINDINGS: Responses from 31 residency program cohorts, including 290 pharmacy residents from a pool of 304 (95.4%) possible respondents, were included in the study. The learner ST was more frequently reported in the top five in pharmacy residents versus student pharmacists (42.8% versus 35.5%, p = 0.022). The woo and communication STs were also more frequently reported in the top five, while the consistency ST was reported less frequently in the top five in pharmacy residents versus student pharmacists (p < 0.05). The executing and relationship building domains had the highest average number of STs (1.58 and 1.56, respectively). DISCUSSION AND SUMMARY: The ST profile of pharmacy residents at residency programs affiliated with four midwestern schools of pharmacy is generally similar to that of pharmacy graduates. However, several STs were more or less prevalent in pharmacy residents. Recognition of these differences may assist residency program directors in marketing and design of programs and ranking of candidates.

Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline Update.

Purpose To update, in collaboration with Cancer Care Ontario (CCO), key recommendations of the American Society of Clinical Oncology (ASCO) guideline on the role of bone-modifying agents (BMAs) in metastatic breast cancer. This focused update addressed the new data on intervals between dosing and the role of BMAs in control of bone pain. Methods A joint ASCO-CCO Update Committee conducted targeted systematic literature reviews to identify relevant studies. Results The Update Committee reviewed three phase III noninferiority trials of dosing intervals, one systematic review and meta-analysis of studies of de-escalation of BMAs, and two randomized trials of BMAs in control of pain secondary to bone metastases. Recommendations Patients with breast cancer who have evidence of bone metastases should be treated with BMAs. Options include denosumab, 120 mg subcutaneously, every 4 weeks; pamidronate, 90 mg intravenously, every 3 to 4 weeks; or zoledronic acid, 4 mg intravenously every 12 weeks or every 3 to 4 weeks. The analgesic effects of BMAs are modest, and they should not be used alone for bone pain. The Update Committee recommends that the current standard of care for supportive care and pain management-analgesia, adjunct therapies, radiotherapy, surgery, systemic anticancer therapy, and referral to supportive care and pain management-be applied. Evidence is insufficient to support the use of one BMA over another. Additional information is available at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .

Evaluation of community pharmacist ability to ensure the safe use of oral anticancer agents: a nationwide survey in Japan.

OBJECTIVES: A recent study of community pharmacists in Canada reported that they required additional education. We conducted a survey of community pharmacists to evaluate the adequacy of education and training in oral anticancer agents in Japan. METHODS: Between May and June 2014, community pharmacists were asked to complete a questionnaire by using two different survey strategies, one online and one via postal mail. RESULTS: Three hundred community pharmacists responded to an online survey and 283 community pharmacists responded to a mailed survey. Only 6-10% of respondents felt that they had received adequate education in oncology or oral chemotherapy. Although 81% of Japanese pharmacists had attended at least one continuing education event related to oncology in the past 2 years, only 54% felt comfortable dispensing oral anticancer agents and only 40% felt comfortable educating patients about oral chemotherapy. In a multivariate analysis, confidence in educating patients about oral chemotherapy was associated with an understanding of chemotherapy cycles and doses (odds ratio = 4.89, 95% confidence interval [2.53-9.45]) and the number of continuing education events they had attended (odds ratio = 1.67, 95% confidence interval [1.35-2.08]). CONCLUSIONS: This is the first report to evaluate whether community pharmacists are equipped to ensure the safe use of oral anticancer agents in Japan. The results are similar to those previously reported for Canadian pharmacists, namely a low rate of positive responses for education in oncology and oral chemotherapy, demonstrating a similar need for additional education and training in oral chemotherapy.

Career Placement of Doctor of Pharmacy Graduates at Eight U.S. Midwestern Schools.

OBJECTIVE: To characterize postgraduation placement plans of 2013 doctor of pharmacy (PharmD) graduates. METHODS: A cross-sectional survey of PharmD graduates from 8 midwestern colleges of pharmacy was designed to capture a comprehensive picture of graduating students' experiences and outcomes of their job search. RESULTS: At graduation, 81% of 2013 respondents had postgraduate plans, with approximately 40% accepting jobs and 40% accepting residencies or fellowships. Eighty-four percent of graduates reported being pleased with offers received, and 86% received placement in their preferred practice setting. Students perceived that securing residencies was more difficult than securing jobs. Students who participated in key activities had a nearly sevenfold increase in successful residency placement. CONCLUSION: While the demand for pharmacists decreased in recent years, responses indicated successful placement by the majority of 2013 graduates at the time of graduation.

Cancer-Associated Venous Thromboembolic Disease, Version 1.2015.

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.

StrengthsFinder Signature Themes of Talent in Doctor of Pharmacy Students in Five Midwestern Pharmacy Schools.

OBJECTIVE: To describe student pharmacists' Signature Themes from the Clifton StrengthsFinder across 5 Midwestern pharmacy institutions and to compare themes by gender, institution, and undergraduate population. METHODS: Student pharmacists completed the StrengthsFinder 2.0 assessment and received their top 5 Signature Themes. Themes were organized and examined by domains (Executing, Influencing, Relationship Building, Strategic Thinking). The distribution of the themes was compared between student pharmacists and undergraduates and themes and domains were compared by institution and gender. RESULTS: Although results varied by institution, the top 5 themes among the 1244 of 1250 students (99.5%) who completed the assessment were: Achiever, Harmony, Learner, Responsibility, and Empathy. Female student pharmacists had more themes in Executing and Relationship Building, while males had more themes in Influencing and Strategic Thinking. Pharmacy students exhibit more Executing domain talents and fewer Influencing domain talents compared with undergraduates. CONCLUSION: Signature Themes were consistent among student pharmacists across 5 Midwestern colleges of pharmacy.

Venous thromboembolic disease.

Venous thromboembolism (VTE) remains a common and life-threatening complication among patients with cancer. Thromboprophylaxis can be used to prevent the occurrence of VTE in patients with cancer who are considered at high risk for developing this complication. Therefore, it is critical to recognize the various risk factors for VTE in patients with cancer. Risk assessment tools are available to help identify patients for whom discussions regarding the potential benefits and risks of thromboprophylaxis would be appropriate. The NCCN Clinical Practice Guidelines in Oncology for VTE provide recommendations on risk evaluation, diagnosis, prevention, and treatment of VTE in patients with cancer.

Reenvisioning assessment for the Academy and the Accreditation Council for Pharmacy Education's standards revision process.

Assessment has become a major aspect of accreditation processes across all of higher education. As the Accreditation Council for Pharmacy Education (ACPE) plans a major revision to the standards for doctor of pharmacy (PharmD) education, an in-depth, scholarly review of the approaches and strategies for assessment in the PharmD program accreditation process is warranted. This paper provides 3 goals and 7 recommendations to strengthen assessment in accreditation standards. The goals include: (1) simplified standards with a focus on accountability and improvement, (2) institutionalization of assessment efforts; and (3) innovation in assessment. Evolving and shaping assessment practices is not the sole responsibility of the accreditation standards. Assessment requires commitment and dedication from individual faculty members, colleges and schools, and organizations supporting the college and schools, such as the American Association of Colleges of Pharmacy. Therefore, this paper also challenges the academy and its members to optimize assessment practices.

Retrospective comparison of filgrastim plus plerixafor to other regimens for remobilization after primary mobilization failure: clinical and economic outcomes.

We performed a retrospective analysis to evaluate clinical and economic outcomes in patients receiving remobilization therapy after primary mobilization failure. Our primary endpoint was to compare filgrastim plus plerixafor to other regimens in their ability to collect a target cell dose of at least 2 million CD34+ cells/kg (cumulative). Of 96 consecutive patients who failed their primary mobilization therapy and in whom a second mobilization was attempted, remobilization consisted of filgrastim plus plerixafor (n = 38), filgrastim with or without sargramostim (n = 43), or chemotherapy plus filgrastim (n = 15), 84% of filgrastim/plerixafor patients were able to collect at least 2 million CD34+ cells/kg from both mobilizations, compared to 60% of patients mobilized with chemotherapy/filgrastim and 79% of the filgrastim ± sargramostim patients (P = 0.17). However, when combined with cells collected from the first mobilization, 53% of filgrastim/plerixafor patients reached the target of 2 million CD34+ cells in one apheresis, compared to 20% of those receiving chemotherapy/filgrastim and 28% of those receiving filgrastim ± sargramostim (P = 0.02). Resource utilization, mobilization drug costs, clinical care costs, and total costs were significantly different. We conclude that while filgrastim/plerixafor is the most efficient remobilization strategy, those clinical benefits may not translate into lower cost, especially when multiple days of plerixafor administration are required.

American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer.

PURPOSE: To update the recommendations on the role of bone-modifying agents in the prevention and treatment of skeletal-related events (SREs) for patients with metastatic breast cancer with bone metastases. METHODS: A literature search using MEDLINE and the Cochrane Collaboration Library identified relevant studies published between January 2003 and November 2010. The primary outcomes of interest were SREs and time to SRE. Secondary outcomes included adverse events and pain. An Update Committee reviewed the literature and re-evaluated previous recommendations. RESULTS: Recommendations were modified to include a new agent. A recommendation regarding osteonecrosis of the jaw was added. RECOMMENDATIONS: Bone-modifying agent therapy is only recommended for patients with breast cancer with evidence of bone metastases; denosumab 120 mg subcutaneously every 4 weeks, intravenous pamidronate 90 mg over no less than 2 hours, or zoledronic acid 4 mg over no less than 15 minutes every 3 to 4 weeks is recommended. There is insufficient evidence to demonstrate greater efficacy of one bone-modifying agent over another. In patients with a calculated serum creatinine clearance of more than 60 mg/min, no change in dosage, infusion time, or interval of bisphosphonate administration is required. Serum creatinine should be monitored before each dose. All patients should receive a dental examination and appropriate preventive dentistry before bone-modifying agent therapy and maintain optimal oral health. Current standards of care for cancer bone pain management should be applied at the onset of pain, in concert with the initiation of bone-modifying agent therapy. The use of biochemical markers to monitor bone-modifying agent use is not recommended.

American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma.

PURPOSE: To update the recommendations for the use of bisphosphonates in the prevention and treatment of bone disease in multiple myeloma. The Update Committee expanded the guideline to include a discussion of osteonecrosis of the jaw (ONJ). METHODS: For the 2007 update, an Update Committee composed of members from the full panel completed a review and analysis of data published since 2002. Searches of Medline and the Cochrane Collaboration Library databases were performed. RECOMMENDATIONS: For multiple myeloma patients who have, on plain radiograph(s) or imaging studies, lytic destruction of bone or spine compression fracture from osteopenia, intravenous pamidronate 90 mg delivered over at least 2 hours or zoledronic acid 4 mg delivered over at least 15 minutes every 3 to 4 weeks is recommended. Clodronate is an alternative bisphosphonate approved worldwide, except in the United States, for oral or intravenous administration. New dosing guidelines for patients with pre-existing renal impairment were added to the zoledronic acid package insert. Although no similar dosing guidelines are available for pamidronate, the Update Committee recommends that clinicians consider reducing the initial pamidronate dose in patients with pre-existing renal impairment. Zoledronic acid has not been studied in patients with severe renal impairment and is not recommended in this setting. The Update Committee suggests that bisphosphonate treatment continue for a period of 2 years. At 2 years, physicians should seriously consider discontinuing bisphosphonates in patients with responsive or stable disease, but further use is at the discretion of the treating physician. The Update Committee also discusses measures regarding ONJ.

American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer.

PURPOSE: To update the 2000 ASCO guidelines on the role of bisphosphonates in women with breast cancer and address the subject of bone health in these women. RESULTS: For patients with plain radiographic evidence of bone destruction, intravenous pamidronate 90 mg delivered over 2 hours or zoledronic acid 4 mg over 15 minutes every 3 to 4 weeks is recommended. There is insufficient evidence supporting the efficacy of one bisphosphonate over the other. Starting bisphosphonates in women who demonstrate bone destruction through imaging but who have normal plain radiographs is considered reasonable treatment. Starting bisphosphonates in women with only an abnormal bone scan but without evidence of bone destruction is not recommended. The presence or absence of bone pain should not be a factor in initiating bisphosphonates. In patients with a serum creatinine less than 3.0 mg/dL (265 mumol/L), no change in dosage, infusion time, or interval is required. Infusion times less than 2 hours with pamidronate or less than 15 minutes with zoledronic acid should be avoided. Creatinine should be monitored before each dose of either agent in accordance with US Food and Drug Administration (FDA) labeling. Oncology professionals, especially medical oncologists, need to take an expanded role in the routine and regular assessment of the osteoporosis risk in women with breast cancer. The panel recommends an algorithm for patient management to maintain bone health. CONCLUSION: Bisphosphonates provide a supportive, albeit expensive and non-life-prolonging, benefit to many patients with bone metastases. Current research is focusing on bisphosphonates as adjuvant therapy. Although new data addressing when to stop therapy, alternative doses or schedules for administration, and how to best coordinate bisphosphonates with other palliative therapies are needed, they are not currently being investigated.

American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma.

PURPOSE: To determine clinical practice guidelines for the use of bisphosphonates in the prevention and treatment of lytic bone disease in multiple myeloma and to determine their respective role relative to other conventional therapies for this condition. METHODS: An expert multidisciplinary Panel reviewed pertinent information from the published literature through January 2002. Values for levels of evidence and grade of recommendation were assigned by expert reviewers and approved by the Panel. Expert consensus was used if there were insufficient published data. The Panel addressed which patients to treat and when to treat them in the course of their disease. Additionally, specific drug delivery issues, duration of therapy, initiation of treatment and management of treatment of lytic bone disease was reviewed and compared with other forms of therapy for lytic bone lesions. Finally, the Panel discussed patient and physician expectations associated with this therapy for bony metastases, as well as public policy implications related to the use of bisphosphonates. The guidelines underwent external review by selected physicians, by the Health Services Research Committee members, and by the ASCO Board of Directors. RESULTS: The available evidence involving randomized controlled trials is modest but supports that oral clodronate, intravenous pamidronate, and intravenous zoledronic acid are superior to placebo in reducing skeletal complications. A reduction in vertebral fractures has consistently been seen across all studies. No agent has shown a definitive survival benefit. Intravenous zoledronic acid has recently been shown to be as effective as intravenous pamidronate. Because there are no direct comparisons between clodronate and pamidronate or zoledronic acid, the superiority of one agent cannot be definitively established. However, the panel recommends only intravenous pamidronate or zoledronic acid in light of the use of the time to first skeletal event as the primary end point and more complete assessment of bony complications in studies evaluating it. Additionally, clodronate is not available in the United States. The choice between pamidronate and zoledronic acid will depend on choosing between the higher drug cost of zoledronic acid, with its shorter, more convenient infusion time (15 minutes), versus the less expensive drug, pamidronate, with its longer infusion time (2 hours). CONCLUSION: Bisphosphonates provide a meaningful supportive benefit to multiple myeloma patients with lytic bone disease. However, further research on bisphosphonates is warranted, including the following: (1) when to start and stop therapy, (2) how to integrate their use with other treatments for lytic bone disease, (3) how to evaluate their role in myeloma patients without lytic bone involvement, (4) how to distinguish between symptomatic and asymptomatic bony events, and (5) how to better determine their cost-benefit consequence.