Retrospective study evaluating immune-related adverse events in cancer patients treated with pembrolizumab.

INTRODUCTION: Pembrolizumab has been on the market for several years, but most of the safety data is based on clinical trials with limited literature evaluating post-marketing immune-related adverse events (irAEs) associated with its use. This study aimed to evaluate the characteristics of irAEs associated with pembrolizumab. METHODS: We included adult patients who had received pembrolizumab between January 2016 and December 2020. The patient electronic profiles and the pharmacy adverse event reporting system were reviewed to identify adverse events. Patients were followed from the start of treatment until 12 months after the last dose, end of the study, or death. The characteristics of the patients and the irAEs were recorded. Univariate and multivariate logistic regression analyses were performed to identify variables associated with the development of irAE. RESULTS: During the study period, 223 patients and 1601 cycles of pembrolizumab were evaluated. A total of 67 irAEs were reported in 58 patients. The median age was 53 years (range 18-84), and most patients were males (75%) with metastatic lung cancer (62%). The most common irAEs were respiratory (30%), followed by gastrointestinal (25%), endocrine (24%), and dermatologic (21%). Among the reported irAEs, 28 were associated with hospital admission, 15 required long-term treatment, and 9 resulted in pembrolizumab discontinuation. In logistic regression, there were no significant predictors associated with irAE. CONCLUSIONS: Respiratory irAEs were the most common in our population. We were unable to identify predictors of irAE in this cohort. Further studies are necessary to identify predictors of adverse events.

Etoposide dosage adjustment in two patients with neuroendocrine tumors and severe liver impairment.

INTRODUCTION: Limited data are available on dosing etoposide in patients with liver impairment. CASE REPORT: We report the dosing strategies for etoposide utilized in two patients with neuroendocrine tumors and severe liver impairment. MANAGEMENT AND OUTCOMES: Treatment consisted of platinum-based chemotherapy regimens, with the decision of whether to administer etoposide and at what doses being based on the liver function before each chemotherapy cycle. By the end of treatment, total bilirubin was normal, and the performance status of both patients had improved, with stable computed tomography scan findings. DISCUSSION: The reported two cases suggest that the administration of etoposide at reduced doses with close monitoring in patients with neuroendocrine tumors and severe liver impairment may still be considered as an option and may improve outcomes.

Critical Review of Double-Carbapenem Therapy for the Treatment of Carbapenemase-Producing Klebsiella pneumoniae.

OBJECTIVE: To review the clinical data on the effectiveness and safety of double carbapenem therapy (DCT) in patients infected with carbapenemase-producing Klebsiella pneumoniae (CP-Kp). DATA SOURCES: A literature search was performed utilizing PubMed and EMBASE (from 1966 to May 2018); bibliographies of the retrieved articles were also searched. STUDY SELECTION AND DATA EXTRACTION: Articles were included if they evaluated patients with infections caused by CP-Kp and were treated with DCT. Meeting abstracts, editorials, and animal and in vitro studies were excluded. DATA SYNTHESIS: The search strategy revealed 8 case reports and 6 clinical studies (total of 171 patients) that evaluated the administration of ertapenem followed by prolonged infusions of meropenem or doripenem. Most patients were critically ill and commonly had infections in the blood, lungs, and urine. Clinical and microbiological success were reported in 70% of the patients and mortality in 24%. Adverse events, which included mostly seizures, sodium disorders, and gastrointestinal symptoms, were reported in 16 patients; none required interruption of treatment. Relevance to Patient Care and Clinical Practice: This review evaluated the clinical experience of DCT in the treatment of CP-Kp infections, based on case reports and clinical studies, for the potential role of DCT as a therapeutic option. CONCLUSION: Despite the limited studies, current data suggest that DCT may be an effective and safe strategy to treat CP-Kp. However, large randomized controlled trials are necessary to clearly define the role of DCT.

Impact of Clinical Pharmacy Services on Patient Management in the Chemotherapy Infusion Clinics: A 5-Year Study at a Comprehensive Cancer Center.

BACKGROUND: Chemotherapy requires careful dosing and monitoring and is associated with numerous adverse events. There is limited data describing the impact of clinical pharmacists in the chemotherapy ambulatory setting. OBJECTIVE: This study aimed to evaluate the impact of clinical pharmacy services on patient management in the adult chemotherapy infusion clinics. METHODS: This was a 5-year retrospective study that utilized the pharmacy electronic documentation system to determine the type of interventions and adverse drug events (ADEs) reported by the clinical pharmacists in the chemotherapy infusion clinics. Interventions were described based on the type of intervention and medication involved. ADEs were evaluated based on the type of ADE, the suspected medication, and the required management. RESULTS: During the study period, 3,279 interventions and 1,445 ADEs were reported. The most common interventions involved dose adjustments (51%), followed by addition (23%) or discontinuation (21%) of prescribed medications. Carboplatin (20%) and zoledronic acid (14%) were the most common medications that required pharmacist interventions. The most common types of ADEs were hematologic (22%) and infusion-related reactions (20%). Docetaxel was the most common medication associated with ADEs (20%). Among the reported ADEs, most required adding supportive care (44%), followed by adjusting chemotherapy doses (22%). CONCLUSION: Clinical pharmacy services at the chemotherapy infusion clinics play an important role in optimizing the chemotherapy regimens as well as identifying and managing ADEs. Future studies should be directed to measure the impact of these services on patient outcomes as well as, physicians and pharmacy operational workload and cost savings.

Effectiveness and Safety of Filgrastim (Neupogen™) versus Filgrastim-aafi (Nivestim™) in Primary Prophylaxis of Chemotherapy-Induced Febrile Neutropenia: An Observational Cohort Study.

BACKGROUND: Despite the demonstrated efficacy and safety of biosimilar filgrastim-aafi (Nivestim™), few studies have compared its use in real-life clinical practice to the originator filgrastim (Neupogen™). OBJECTIVES: This study aimed to compare the effectiveness and safety of filgrastim and filgrastim-aafi for the primary prophylaxis of chemotherapy induced-febrile neutropenia in the real-life setting. PATIENTS AND METHODS: A retrospective cohort study included all adult cancer patients at the King Hussein Cancer Centre requiring primary prophylaxis for chemotherapy-induced febrile neutropenia between 2014 and 2016. Two cohorts were selected: patients who received filgrastim and those who received filgrastim-aafi. The primary endpoint was the incidence of febrile neutropenia; the secondary endpoints were the incidence of adverse drug reactions (ADRs), hospital admissions due to febrile neutropenia, and the mean length of hospitalization. Chi-squared tests were performed to evaluate differences between groups. Logistic regression was conducted to adjust for confounding factors. RESULTS: A total of 268 patients were identified, with 88 in the filgrastim cohort and 180 in the filgrastim-aafi cohort; 64%were females. The mean age was 47 (±15) years. The incidence of febrile neutropenia was 21.6% in the filgrastim cohort and 15% in the filgrastim-aafi cohort (P = 0.179). No statistically significant differences were detected in the incidence of hospital admission (P = 0.551) or ADRs (P = 0.623) between the two cohorts. Upon adjusting for the confounding factors, results remained statistically insignificant. CONCLUSION: Filgrastim and filgrastim-aafi had comparable effectiveness and safety as primary prophylaxis for chemotherapy-induced febrile neutropenia. More extensive prospective studies with additional insight on the cost implications are required.

Comparing the Incidence of Febrile Neutropenia Resulting in Hospital Admission Between the Branded Docetaxel and the Generic Formulations.

Studies have raised concern about the safety of generic compared with branded drugs. Febrile neutropenia (FN) resulting in hospital admission was compared between the branded docetaxel (Taxotere®, Sanofi) and 2 generic formulations (docetaxel Ebewe and docetaxel Hospira) in patients with breast cancer. This was a retrospective study that included patients with breast cancer who received docetaxel between January 2012 and December 2014. Patients who had an admission diagnosis of FN and had received docetaxel within 14 days prior to admission were evaluated. The docetaxel brand and dose, patient characteristics, hospital length of stay, admission to the intensive care unit (ICU), and mortality were recorded. During the study period, 2904 cycles of docetaxel were given for 876 patients (1519 cycles of docetaxel Sanofi, 811 cycles of docetaxel Hospira, and 574 cycles of docetaxel Ebewe). Among the cycles given, 130 cycles were associated with FN that required hospital admission. The overall incidence of FN resulting in hospital admission was significantly higher in patients who had received docetaxel Hospira, compared with patients who had received docetaxel Sanofi (47[5.8%] cycles vs 53 [3.5%] cycles, P = .009), but there was no significant difference between docetaxel Ebewe and docetaxel Sanofi (30[5.2%] cycles vs 53 [3.5%] cycles, P = .069). All cases of FN resolved except for 1 patient who died in the ICU after receiving docetaxel Ebewe. There was a significant difference in the incidence of FN between docetaxel Sanofi and docetaxel Hospira, but all cases in both groups resolved completely.