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.

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.

Granulocyte colony-stimulating factor utilization postautologous hematopoietic stem cell transplant in multiple myeloma patients: Does one size fit all?

PURPOSE: To evaluate a single institution's experience with granulocyte colony-stimulating factor after autologous hematopoietic stem cell transplant in myeloma patients to identify populations that benefit most from granulocyte colony-stimulating factor administration. METHODS: Retrospective chart reviews were conducted on patients 18+ years with multiple myeloma that underwent autologous hematopoietic stem cell transplant at UW Health from January 2012 to May 2016. Data collection included demographics, length of stay, time to engraftment, Eastern Cooperative Oncology Group performance status score, and hematopoietic cell transplantation-comorbidity index. The primary outcome was days from transplant to engraftment, defined as absolute neutrophil count > 500/mm3 for two consecutive days or absolute neutrophil count > 1000/mm3 once. A subset analysis was performed on patients whose date of engraftment was known. RESULTS: In total, 216 individual patients were included in the full cohort and 122 patients included in the subset analysis. Median time to engraftment between patients administered granulocyte colony-stimulating factor and the nongranulocyte colony-stimulating factor group was 12 versus 19 days (P < 0.001) in the full cohort and 12 versus 14 days (P < 0.001) in the subset analysis. The average length of stay posthematopoietic stem cell transplant in the granulocyte colony-stimulating factor group was 15 days versus 17 days in the nongranulocyte colony-stimulating factor group (P = 0.026) in the subset analysis. Additionally, no difference in time to engraftment was seen when stratified by age, Eastern Cooperative Oncology Group performance status score, or hematopoietic cell transplantation-comorbidity index. CONCLUSION: Our study supports use of granulocyte colony-stimulating factor posthematopoietic stem cell transplant in myeloma patients to decrease time to engraftment and length of stay. Consideration should be given to utilization in all patients in this population posthematopoietic stem cell transplant. Further research is needed to identify the populations that benefit most from granulocyte colony-stimulating factor administration.