A Phase 2 Trial of Nab-paclitaxel in Combination With Anti-PD1 Therapy in Advanced Urothelial Cancer.

PURPOSE: Immune checkpoint inhibitor therapy and nab-paclitaxel have each shown efficacy in platinum-refractory advanced urothelial cancer. We conducted a single-arm phase 2 trial of the combination of nab-paclitaxel and pembrolizumab in platinum-refractory or cisplatin-ineligible advanced urothelial cancer (NCT03240016). MATERIALS AND METHODS: Eligible patients had RECIST 1.1 measurable and cisplatin-ineligible or platinum-refractory advanced urothelial cancer. Patients received nab-paclitaxel at starting dose of 125 mg/m2 intravenously on days 1 and 8 and pembrolizumab 200 mg intravenously on day 1 in 21-day cycles until progression, intolerable toxicity, or death. Nab-paclitaxel was permitted to be discontinued after 6 cycles. The nab-paclitaxel starting dose was reduced to 100 mg/m2 after planned interim analysis. Primary end point was overall response rate by RECIST 1.1. Secondary end points included safety/toxicity, duration of response, progression-free survival), and overall survival. RESULTS: Between February 2018 and April 2021, 36 response-evaluable patients were enrolled. There was an equal split of platinum-refractory and cisplatin-ineligible patients. Confirmed overall response rate was 50.0% (18/36) including 3 complete and 15 partial responses; 31/36 patients experienced some tumor shrinkage. At a median follow-up of 19.7 months, median duration of response was 4.4 months (95% CI: 4.0-8.6), median progression-free survival 6.8 months (95% CI: 4.4-not reached), and median overall survival 18.2 months (95% CI: 10.6-not reached). Grade ≥3 adverse events occurred in 21/36 patients including fatigue (n=6) and anemia (n=4). Ten patients had immune-mediated adverse events. CONCLUSIONS: The combination of nab-paclitaxel and pembrolizumab exhibited promising activity in advanced urothelial cancer and warrants further study in this population. After reduction in nab-paclitaxel starting dose, no unanticipated or unexpected toxicities emerged.

Cancer Drug Safety Training: Comparing Distance and In-Person Simulations for Interprofessional Education.

The Multi-Professional Oncology Safety and Simulation Training (MOSST) program, supported by the National Cancer Institute was launched in Fall 2018. The original workshop was conducted in person. As the COVID pandemic hit the program was transitioned to an online/distance simulation program using best practices in healthcare simulation design and implementation. The full day workshop was moved to an online platform using Zoom and the in-person simulations were re-developed as video branching case simulations. Learner outcomes that were identical in each modality were evaluated using the evaluation metrics from the original workshop. The use of a distance simulation modality to deliver the MOSST workshop resulted in a high-quality educational experience for the learners and the educational outcomes were comparable to the in-person version. Distance simulation using virtual unfolding case studies and didactic content showed comparable subjective and objective outcomes from participating learners. This work adds to the developing body of research on distance simulation.

Treatment related toxicities with combination BRAF and MEK inhibitor therapy in resected stage III melanoma.

Combination dabrafenib (D) and trametinib (T) is an FDA approved adjuvant therapy for patients with resected stage III BRAF-mutant melanoma. We describe treatment-related toxicities with adjuvant D+T in a real-world population through a retrospective case series. The primary endpoint was development of toxicities. Results: Eighteen of the 20 patients (90%) required at least one treatment interruption due to adverse events (AEs), 11 patients (55%) required a dose reduction and 13 (65%) permanently discontinued therapy due to an AE. The nine patients who did not require dose reduction had been initiated on a lower starting dose of dabrafenib. The most common treatment-limiting AEs were recurrent pyrexia and chills (85%) and liver laboratory abnormalities (50%). The median total time on therapy was 148.5 days (range 19-383), 40.7% (range 5.2-100%) of the intended one-year duration. Conclusion: Adjuvant treatment of melanoma with combination D+T is associated with treatment-limiting toxicities in the majority of this patient group. Patients should be carefully monitored throughout therapy.

Implementation and outcomes of a pharmacist-led collaborative drug therapy management program for oncology symptom management.

INTRODUCTION: Nausea, vomiting, constipation, and diarrhea are common cancer and cancer therapy adverse effects. Pharmacists are uniquely positioned to optimize patient symptom control and minimize excess use of hospital resources, such as emergency department visits. METHODS: Michigan Medicine oncology clinical pharmacists have been independently providing patient symptom management through a collaborative drug therapy management (CDTM) program which established guidelines for management of gastrointestinal toxicities (nausea, vomiting, diarrhea, and/or constipation) secondary to a patient's cancer diagnosis or treatment of the cancer. Patients were referred to the pharmacist by the treating oncologist or hematologist. RESULTS: From June 2019 to May 2020, there were a total of 62 patient referrals. Ten of the 62 referrals did not meet the CDTM inclusion criteria, resulting in 52 patients who were managed by the pharmacists. The total number of individual pharmacist visits was 136, with a median of 2.2 (range, 0-11) visits per patient referred. A total of 169 categorized pharmacist interventions were captured. Most interventions (100/169, 59.2%) were related to nausea/vomiting. Diarrhea-related and constipation-related interventions accounted for 10 (5.9%) and 13 (7.7%) of the total interventions, respectively. Most patients (36/52, 69.2%) had a reduction in the severity of their referral diagnosis symptom(s) based on Common Terminology Criteria for Adverse Events grading. CONCLUSION: The Michigan Medicine Pharmacist CDTM program allowed pharmacists to independently manage gastrointestinal toxicities of patients with cancer and improved patient symptom severity. The CDTM program has the opportunity to improve quality of care.

Chemotherapy Remote Care Monitoring Program: Integration of SMS Text Patient-Reported Outcomes in the Electronic Health Record and Pharmacist Intervention for Chemotherapy-Induced Nausea and Vomiting.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a common cause of unplanned healthcare utilization. The University of Michigan Rogel Cancer Center initiated the chemotherapy remote care monitoring program (CRCMP) to proactively identify patients experiencing CINV and intervene before the need for urgent evaluation. METHODS: High-risk patients for CINV are identified by neurokinin-1 (NK-1) antagonist administration, enrolled in the CRCMP, and received a daily text message survey for 7 days after chemotherapy administration to report symptoms. Responses above a set threshold trigger a message to the team pharmacist for intervention. The primary outcome of 14-day unplanned healthcare use was evaluated before and after CRCMP implementation. RESULTS: In 8 months, 652 patients received an NK-1 antagonist (2,244 cycles) and 387 patients were enrolled in the CRCMP (59%). Text message response rate was 94%. Clinical pharmacists provided 248 interventions in 121 patient episodes meeting threshold criteria. Fourteen-day unplanned healthcare use was decreased in the CRCMP-enrolled NK-1 episodes (6.68% v 4.53%, P = .02). Admissions were numerically lower for those enrolling in CRCMP when only admissions for nausea were considered (0.63% v 0.35%, P = .33). CONCLUSION: The CRCMP allowed for real-time management of patient-reported CINV symptom burden based on patient-reported outcomes (PROs) and an electronic medical record-integrated SMS text questionnaire. Clinical pharmacists were key team members to manage patient symptoms. Enrollment in CRCMP significantly reduced overall unplanned healthcare utilization. Although these changes were numerically small, any reduction in unnecessary care utilizing PROs can contribute to high-value care for patients with cancer.

Evaluation of an Interprofessional Training Program to Improve Cancer Drug Therapy Safety.

PURPOSE: Drug therapy for cancer is a high-risk, high-volume clinical intervention that requires interprofessional teams. Given the complexity of anticancer drug therapy and safety concerns, an interdisciplinary team developed a novel training program for oncology registered nurses and pharmacists to improve cancer drug safety. METHODS: Participants completed preworkshop learning assessments and received access to web-based modules on six topics: hazardous drug handling, drug extravasation, hypersensitivity reaction management, sepsis recognition, immune checkpoint inhibitor toxicities, and oral oncolytic adherence. In a 7-hour workshop, participants applied module content in interactive exercises and high-fidelity simulations. Preworkshop and postworkshop questionnaires assessed changes in knowledge and confidence in each topic. Program satisfaction and changes to clinical practice or policies were assessed 3 months after the workshop. RESULTS: Two hundred ninety-two nurses and 82 pharmacists applied to participate, and 103 (35%) and 44 (54%) have participated, respectively. Long-term follow-up data were available on 133 (90%) participants. Change scores in confidence to meet program objectives increased between pre- and postworkshop (range of increase 0.6-0.8, P < .01). Knowledge scores increased significantly between pre- and postworkshop (average improvement of 3.2 points, P < .01). Overall program satisfaction was high (mean 5.0, standard deviation [0.2] on a five-point scale). Seventy-seven (60%) reported that they had made at least one clinical practice or institutional policy change at 3 months. CONCLUSION: An interprofessional education program with online modules, in-person interactive sessions, and simulation activities is a promising strategy to deliver cancer drug safety content to practicing oncology clinicians.

Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma.

Background Pazopanib is approved for metastatic renal cell carcinoma (RCC). We assessed the safety and efficacy of pazopanib with a low fat meal (LFM): <400 cal and < 20% fat or 10 g per meal. Methods A single arm study of pazopanib with a LFM in 16 adult patients with metastatic RCC with a clear cell component, RECIST 1.1 measurable disease, ECOG PS ≤ 2, and ≤ 3 prior therapies. Pazopanib at 400 mg daily given with LFM for 12 weeks. Incremental dose increases up to 800 mg, or irreversible decreases to 200 mg, allowed every 2 weeks. Primary study endpoint was safety; adverse events (AE) measured per CTCAE version 4.0. Secondary endpoints of RECIST 1.1 response with assessment as 12 weeks; pharmacokinetic (PK) analysis at nine time points, and CYP3A4 polymorphism evaluation. Results Pazopanib with a LFM was well tolerated; 13 of 16 subjects completed all 12 weeks. Three patients withdrew due to adverse events (AEs), with five occurrences of grade 3 AEs. Conclusions Pazopanib with a LFM has acceptable safety and comparable efficacy to fasting administration. Total median pazopanib dose per subject for the study duration was 63.5% of maximum possible conventional dose. A larger study is warranted. Clinical Trial Registration Number: NCT02729194.

Comparison of Nine Tools for Screening Drug-Drug Interactions of Oral Oncolytics.

PURPOSE: Patients with cancer are an especially vulnerable population to potential drug-drug interactions (DDIs). This makes it important to adequately screen them for DDIs. The objective of this study was to compare the abilities of nine DDI screening tools to detect clinically relevant interactions with oral oncolytics. METHODS: Subscription-based tools (ie, PEPID, Micromedex, Lexicomp, Facts & Comparisons) and free tools (ie, Epocrates Free, Medscape, Drugs.com, RxList, WebMD) were compared for their abilities to detect clinically relevant DDIs for 145 drug pairs including an oral oncology agent. Clinical relevance was determined by a pharmacist using Stockley's Drug Interactions. Descriptive statistics were calculated for each tool, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and then compared grouped by free or subscription-based tools for the secondary analysis and analyzed via generalized estimating equations. RESULTS: For individual metrics, PPV had overall higher values (0.88 to 0.97) relative to the low values included for sensitivity (0.65 to 0.96), specificity (0.53 to 0.93) and NPV (0.38 to 0.83). The top-performing subscription and free tools, Lexicomp and Drugs.com, had no statistically significant differences in performance. Overall, subscription tools had a significantly higher sensitivity (0.85 ± 0.017 v 0.78 ± 0.017; P = .0082) and NPV (0.57 ± 0.039 v 0.48 ± 0.032; P = .031) than free tools. No differences were observed between the specificity and PPV. CONCLUSION: Due to the low performance of some tools for sensitivity, specificity, and NPV, individual performance should be examined and prioritized on the basis of the intended use when selecting a DDI tool. If a strong-performing subscription-based tool is unavailable, a strong-performing free option, like Drugs.com, is available.

Evaluation of outpatient medication reconciliation involving student pharmacists at a comprehensive cancer center.

OBJECTIVE: To determine the number of discrepancies and medication-related problems found as a result of pharmacy-led medication reconciliation involving introductory pharmacy practice experience (IPPE) students at a comprehensive cancer center. SETTING: Outpatient infusion center of a National Cancer Institute (NCI)-designated and National Comprehensive Cancer Network (NCCN) cancer center. PRACTICE DESCRIPTION AND INNOVATION: Third-year IPPE students contacted and completed medication reconciliation for 510 hematology/oncology patients scheduled for infusion center appointments without a coupled provider visit. IPPE students discussed the findings of the medication reconciliations with their pharmacist preceptors, who updated the medication histories in the electronic medical record (EMR) and communicated with prescribers directly about identified medication-related problems. All medication reconciliation was documented using a standardized note template in the EMR. MAIN OUTCOME MEASURES: Number of medication discrepancies found, including medication additions, medication deletions, dose changes, and herbal product additions; medication-related problems-including drug-drug interactions, untreated indications (e.g., nausea, vomiting, pain, need for prophylactic medications), failure of patients to receive prescribed medications, and adverse drug reactions-were also documented. RESULTS: Medication reconciliation was completed for 510 patients through the student pharmacist/pharmacist preceptor-led intervention during a 1-year period between January 1, 2013, and December 31, 2013. A total of 88% of patients had at least one discrepancy identified in their medication history and corrected in the EMR. In addition, 11.4% of patients had a medication-related problem identified. CONCLUSIONS: Pharmacy-led medication reconciliation identified a large number of discrepancies among our hematology/oncology patients. This intervention allowed for correction of discrepancies in the EMR leading to improved accuracy of patient medication lists. In addition, it provided a valuable learning experience for student pharmacists.

Procarbazine and antidepressants: a retrospective review of the risk of serotonin toxicity.

BACKGROUND: Procarbazine is an anticancer agent that also inhibits monoamine oxidase, an enzyme responsible for the metabolism of various catecholamines, including serotonin. METHODS: A retrospective chart review of lymphoma patients who were treated with both procarbazine and an antidepressant, as well as procarbazine alone, was performed to determine if signs and symptoms of serotonin toxicity were present. RESULTS: A total of 65 patients received procarbazine between 2004 and 2010 and were eligible to be included in the study. Twenty-six of these patients received an antidepressant in combination with procarbazine, with selective serotonin reuptake inhibitors being the most common type of antidepressant. No patients in the study were diagnosed with serotonin toxicity, nor did any meet Hunter's diagnostic criteria for serotonin toxicity. Diarrhea, tremor, and shivering were the symptoms from Sternbach's criteria that were further analyzed, with diarrhea occurring 8.54% of the time, tremor occurring 5.53% of the time, and shivering occurring 2.51% of the time in patients who received an antidepressant with their procarbazine. Despite these symptoms, the diagnosis of serotonin toxicity according to Sternbach's criteria was determined to be unlikely. CONCLUSIONS: In this small sample of patients treated with procarbazine plus an antidepressant (most typically SSRIs), there were no reports of serotonin toxicity, nor did any patients demonstrate symptoms consistent with serotonin toxicity. The authors urge clinicians to ensure depression is adequately managed in cancer patients who are undergoing procarbazine therapy, starting with typical first-line antidepressant agents.

Outcomes of therapy: vancomycin-resistant enterococcal bacteremia in hematology and bone marrow transplant patients.

PURPOSE: The purpose of this study was to evaluate the risk factors associated with the treatment failure and 30-day mortality in hematology and bone marrow transplant patients treated with daptomycin or linezolid for vancomycin-resistant enterococci (VRE) bacteremia. The safety and tolerability of therapy was also assessed. METHODS: This single-center, retrospective study included adult patients admitted to the hematology or bone marrow transplant service with documented vancomycin-resistant Enterococcus faecium or Enterococcus faecalis bacteremia and received at least 48 h of either linezolid or daptomycin as primary treatment. Clinical and microbiologic outcomes were assessed at day 7, 14, and 30 of hospital stay. RESULTS: A total of 72 patients were included in the analysis. Forty-three patients received daptomycin as primary treatment and 29 received linezolid as primary treatment. Overall success rate at day 7 was 81.9%, day 14 success rate was 79.2%, and day 30 success rate was 76.4% for all patients. Forty-one patients (57.0%) had high-grade bacteremia defined as greater than one positive blood culture for VRE. The mortality rate was significantly higher if high-grade bacteremia was present (34.1% vs. 7.0%; p = 0.009). CONCLUSIONS: This study suggests that linezolid and daptomycin are both reasonable options for treating VRE bacteremia in hematology and bone marrow transplant patients; however, patients with high-grade VRE bacteremia may be at increased risk for treatment failure.