Clinical utility of a regional precision medicine molecular tumor board and challenges to implementation.

PURPOSE: Molecular tumor boards provide precision treatment recommendations based on cancer genomic profile. However, practical barriers limit their benefits. We studied the clinical utility of the precision medicine molecular tumor board (PMMTB) and described challenges with PMMTB implementation. METHODS: An observational cohort study included patients reviewed by the PMMTB between September 2015 to December 2017. Patients who had consented to the registry study were included. The primary endpoint of this study was time on treatment (ToT) ratio. Clinical utility was established if the primary endpoint had least 15% of patients achieving a ToT ratio of ≥1.3. RESULTS: Overall, 278 patients were presented to the PMMTB and 113 cases were included in the final analysis. The PMMTB identified at least one nonstandard of care (SOC) clinically actionable mutation for 69.0% (78/113) of cases. In patients who received non-SOC treatment, 43.8% (7/16) achieved a ToT ratio of 1.3 or more (p < 0.001). Fifty-nine patients did not receive non-SOC recommendations. Reasons for not pursuing treatment included 35.6% having response to current treatment, 20.3% died prior to starting or considering PMMTB recommendations, 13.6% pursued other treatment options based on clinician discretion, another 10.2% pursued other treatment options because clinical trials recommended were not geographically accessible, 8.5% had rapid decline of performance status, 6.8% lacked of financial support for treatment, and 5.1% were excluded from clinical trials due to abnormal laboratory values. CONCLUSION: The regional PMMTB non-SOC recommendations benefitted a majority of patients and additional processes were implemented to assist with non-SOC treatment accessibility.

Implementation of a clinical pharmacist-led service to optimize management of refractory chemotherapy-induced nausea and vomiting in adult hematology/oncology clinic.

OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) is a common and potentially debilitating adverse effect of chemotherapy. Refractory CINV can be particularly difficult to control. This report provides details on the implementation and evaluation of a pharmacist-led program for the management of refractory CINV in hematology and oncology clinics. METHODS: A pharmacist-led program open to adult outpatients with refractory CINV was implemented at University of Wisconsin. Pharmacists conducted baseline and follow-up assessments, provided patient education, and started, discontinued, and/or adjusted antiemetics as clinically necessary for all enrolled patients. Retrospective chart review was used to describe the proportion of patients whose CINV improved through pharmacist intervention, effect of the program on antiemetic adherence, categorization of pharmacist interventions, and duration of patient enrollment. RESULTS: Forty-six patients were enrolled between February 2019 and January 2020. Forty-one patients (89.1%) had an overall reduction in their nausea and vomiting from baseline. Eleven patients (23.9%) met criteria for nonadherence to prescribed antiemetics at baseline; all patients were adherent at unenrollment. A total of 111 pharmacist interventions were made. The most common intervention was addition of new breakthrough antiemetic. The least common intervention was dose escalation of a previously prescribed antiemetic. The average number of interventions made per patient was 2.5. On average, patients were enrolled in the program for 16.6 days and met with a pharmacist three times. CONCLUSION: Implementation of this program standardized and streamlined pharmacist involvement with refractory CINV. Enrollment resulted in a measurable reduction in nausea and/or vomiting for patients with refractory CINV.

Unleashing the power of immunotherapy and targeted therapy combinations: Advancing cancer care or discovering unknown toxicities?

OBJECTIVE: The purpose of this review was to summarize the triumphs and pitfalls of tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) combinations.Data sources: A literature review of PubMed was conducted and studies were included if they were classified as a clinical trial and assessed TKI and ICI combinations for solid tumor malignancies. Dates of literature search included January 1, 1988 through September 22, 2019.Data summary: In the past decade, TKI and ICI monotherapy strategies have changed the management of many advanced solid tumors through their unique mechanisms of action. Preclinical data suggests that TKIs may be able to sensitize tumors to ICI therapy via direct and indirect pathways; however, optimal mechanisms to support various TKI and ICI combinations have yet to be determined. The FDA recently approved TKI and ICI combinations for renal cell carcinoma, endometrial carcinoma, and melanoma. Several other tumor types currently have TKI and immunotherapy combinations under investigation with mixed results. Dual therapy with TKIs and immunotherapy have the potential to be synergistic and improve patient outcomes; however, careful consideration will need to be taken in regard to what TKI and immunotherapy are combined. CONCLUSIONS: Future research will be needed to determine appropriate sequencing of TKIs and ICIs after progression on combination therapy. Continued research is necessary to determine optimal dual TKI and immunotherapy options.

Hypertension and QT interval prolongation associated with targeted systemic cancer therapies.

OBJECTIVE: To summarize the proposed mechanisms behind hypertension and QT interval prolongation associated with use of targeted systemic cancer therapies and provide recommendations for monitoring or managing these toxicities. SUMMARY: The cardiotoxic effects of targeted systemic cancer therapies represents a new paradigm of cancer treatment associated cardiovascular adverse events. National guidelines regarding optimal monitoring and management strategies for hypertension and QT interval prolongation associated with use of these therapies are lacking. While the pathophysiological drivers of hypertension due to targeted systemic cancer therapies differ by class of targeted therapy, general management strategies do not. Routine blood pressure monitoring throughout the duration of therapy is recommended for all agents. Patients who experience hypertension often can be treated with the addition or modification of antihypertensive therapies. Uncontrolled hypertension despite optimal medical management may require dose modifications or discontinuation of the targeted systemic cancer therapy. Electrocardiogram monitoring is recommended for patients who receive targeted therapies that may prolong the QT interval. Minimizing or managing drug interactions with other QT prolonging medications is recommended in addition to ensuring adequate electrolyte supplementation. Dose modifications or discontinuation of the targeted systemic therapy may be necessary for patients who experience QT interval prolongation. CONCLUSIONS: Appropriate cardiovascular monitoring and timely management of treatment-emergent toxicities can optimize therapy for patients receiving targeted systemic cancer therapies associated with a risk of drug-induced hypertension or QT interval prolongation.

Implementation of a chemotherapy stewardship process.

PURPOSE: To design and implement a chemotherapy stewardship process to optimize the location of chemotherapy administration in an effort to decrease the number of inappropriate inpatient anticancer regimen administrations and decrease institutional costs associated with inpatient administration. SUMMARY: As the costs of anticancer agents continue to rise, it is crucial that multidisciplinary efforts are aimed at managing anticancer medication utilization; this is especially important for high-cost medications, medications whose use requires increased monitoring due to safety concerns, and medications that do not exert effects quickly and, as such, can be more appropriately administered in the outpatient setting. It is imperative that pharmacists play a role in managing chemotherapy medication utilization, as pharmacists provide expertise in formulary management, a vast knowledge of financial impact and reimbursement processes, and clinical knowledge that can help predict the expected effectiveness and adverse effects of each anticancer regimen. Our institution sought to develop and implement a multidisciplinary chemotherapy stewardship program targeting the optimization of site of anticancer agent administration with a goal of decreasing both cost and inappropriate utilization of high-cost, high-risk anticancer agents. CONCLUSION: Implementation of a chemotherapy stewardship service may decrease the number of inappropriate inpatient anticancer regimen administrations and decrease inpatient resource use, thereby decreasing costs to institutions. The concept of a chemotherapy stewardship process was well received by multidisciplinary healthcare colleagues, and a collaborative approach should be used to design and implement such processes.

PARP-inhibitor potpourri: A comparative review of class safety, efficacy, and cost.

Purpose: To summarize similarities and differences in efficacy, safety, and cost of available PARP-inhibitors and offers pearls to distinguish subtle nuances between each agent to help guide therapy. Summary: Currently, four PARP-inhibitors (olaparib, rucaparib, niraparib, and talazoparib) are FDA-approved, with olaparib, rucaparib, and niraparib approved for treatment and/or maintenance or ovarian cancer and olaparib and talazoparib approved for the treatment of recurrent metastatic BRCA-mutant, HER2-negative breast cancer. While the PARP-inhibitor class is generally are well-tolerated, each agent does possess a unique side-effect profile. Niraparib and talazoparib have more prominent hematologic adverse event profiles, while niraparib has an increased risk of cardiac events. In patients using other medications with known drug interactions, niraparib may be the preferred option for patients with ovarian cancer, and talazoparib may be the preferred option for patients with breast cancer because neither of these agents undergo hepatic metabolism. These agents also can incur large financial toxicities for patients, and olaparib currently has the broadest range of options for financial assistance. Conclusion: Although these agents have similar approved indications, efficacy, and toxicity profiles, there are notable differences that may help direct choice of therapy and optimize treatment for patients. It is important to incorporate patient-specific factors to optimize PARP-inhibitor therapy for patients.

Automated parenteral chemotherapy dose-banding to improve patient safety and decrease drug costs.

PURPOSE: To improve patient safety and reduce drug waste through implementation of automated parenteral chemotherapy dose-banding within an electronic health record. METHODS: Parenteral chemotherapy dose-rounding practices were transitioned from a manual, pharmacist-driven workflow to an automated process within the electronic health record. Initial medications transitioned included bevacizumab, rituximab, and trastuzumab. Dose-banding tables were built to standardize rounding within a 10% parameter and then subsequently incorporated into the electronic health record after receiving multidisciplinary approval. Following implementation, a retrospective chart review was performed to compare drug and associated cost savings with manual dose-rounding and automated dose-banding. Medication safety improvements were measured by comparing the change in the number of clicks needed for pharmacist verification as well as by evaluation of submissions to our event reporting system. RESULTS: After implementing automated parenteral chemotherapy dose-banding, reported medication errors associated with the parenteral chemotherapy rounding process decreased. The number of event submissions related to incorrect rounding decreased from four submissions in the pre-implementation period to zero in the post-implementation period. Automation saved pharmacists at least 9,297 additional clicks and 11,363 additional keystrokes and also led to notable increases in total drug savings as well as drug cost savings. CONCLUSION: Overall safety of our parenteral chemotherapy ordering processes within our electronic health record was improved after the implementation of automated dose-banding. By standardizing the administered doses for three chemotherapy agents, we were also able to increase total drug savings and associated drug cost savings.

Expansion of pharmacist clinical services to optimize the management of immune checkpoint inhibitor toxicities.

INTRODUCTION: The development of immune checkpoint inhibitors has revolutionized cancer treatment and is now a part of the treatment paradigm for several malignancies. Although immune checkpoint inhibitors are generally well tolerated, treatment is associated with immune-related adverse events, some serious and potentially life threatening. Early identification and prompt appropriate management of immune-related adverse events are crucial to prevent morbidity and mortality. The complexity and severity of immune-related adverse events require interdisciplinary collaboration to optimize care. Patient and caregiver education and continued communication between patients and members of the oncology care team are vital for timely recognition and successful management of immune-related adverse events. The objective of this program is to provide a proof of concept; a pharmacist-led immune checkpoint inhibitor management program will increase early recognition and management of immune-related adverse events through patient and caregiver education and proactively assessing patients for toxicities. METHODS: At the University of Wisconsin Carbone Cancer Center, we developed and implemented a pharmacist-driven program, referred to as the immune checkpoint inhibitor program, which aimed to ensure patient and caregiver education and continuous monitoring of immune-related adverse events. This program utilized pharmacist-patient encounters to improve patient and caregiver education and follow-up monitoring. The design and implementation are detailed. Pharmacist interventions and patient outcomes were evaluated. RESULTS: At interim analysis, 47 patients were enrolled in the program and pharmacists completed 34 interventions on 26 patients. Pharmacists are well positioned to educate patients and caregivers on immune checkpoint inhibitor therapy and provide proactive monitoring to detect immune-related adverse events. We hypothesize that the interventions made by pharmacist may lead to earlier recognition and treatment of immune-related adverse events.

Implementing value assessment in oncology practice: A single-center experience.

Cancer treatment costs in the United States are rising. Evidence suggests that increased costs do not always correlate with improved outcomes. Several organizations have developed tools and frameworks to assess cancer treatment value; however, many centers have reported difficulty in implementing these tools and effectively incorporating value-based decision making into clinical practice. After evaluating existing frameworks, the Carbone Cancer Center at UW Health set out to create a value-based tool that could be used to inform the decisions of clinicians and patients. This tool was piloted in metastatic or advanced non-small cell lung cancer, specifically in the second-line setting to assess the value of immune checkpoint inhibitors nivolumab, atezolizumab, and pembrolizumab. The results of the pilot suggest that atezolizumab is the best value of the three agents in this patient population. Challenges and opportunities for improvement that were identified during the pilot process have helped refine the tool for use in a variety of disease states within oncology.

Multidisciplinary Optimization of Oral Chemotherapy Delivery at the University of Wisconsin Carbone Cancer Center.

PURPOSE: Use of oral chemotherapy is expanding and offers advantages while posing unique safety challenges. ASCO and the Oncology Nursing Society jointly published safety standards for administering chemotherapy that offer a framework for improving oral chemotherapy practice at the University of Wisconsin Carbone Cancer Center. METHODS: With the goal of improving safety, quality, and uniformity within our oral chemotherapy practice, we conducted a gap analysis comparing our practice against ASCO/Oncology Nursing Society guidelines. Areas for improvement were addressed by multidisciplinary workgroups that focused on education, workflows, and information technology. Recommendations and process changes included defining chemotherapy, standardizing patient and caregiver education, mandating the use of comprehensive electronic order sets, and standardizing documentation for dose modification. Revised processes allow pharmacists to review all orders for oral chemotherapy, and they support monitoring adherence and toxicity by using a library of scripted materials. RESULTS: Between August 2015 and January 2016, revised processes were implemented across the University of Wisconsin Carbone Cancer Center clinics. The following are key performance indicators: 92.5% of oral chemotherapy orders (n = 1,216) were initiated within comprehensive electronic order sets (N = 1,315), 89.2% compliance with informed consent was achieved, 14.7% of orders (n = 193) required an average of 4.4 minutes review time by the pharmacist, and 100% compliance with first-cycle monitoring of adherence and toxicity was achieved. CONCLUSION: We closed significant gaps between institutional practice and published standards for our oral chemotherapy practice and experienced steady improvement and sustainable performance in key metrics. We created an electronic definition of oral chemotherapies that allowed us to leverage our electronic health records. We believe our tools are broadly applicable.