Assessing the use of anti-PD1 monotherapy as adjuvant therapy and determinants of treatment choice in stage III cutaneous melanoma in the US.

BACKGROUND: The objective of this study was to describe real-world adjuvant therapy (AT) use by disease substage and assess determinants of treatment choice among patients with stage III melanoma. METHODS: This non-interventional retrospective study included survey responses and data from patient records provided by US medical oncologists. Survey responses, patient demographic/clinical characteristics, treatment utilization, and reasons for treatment were reported descriptively. The association between patient and disease characteristics and AT selection was assessed using logistic and multinomial regression models, overall and stratified by AJCC8 substage (IIIA vs. IIIB/C/D) and type of AT received (anti-PD1 monotherapy, BRAF/MEK, no AT), respectively. RESULTS: In total 152 medical oncologists completed the survey and reviewed the charts of 507 patients (168 stage IIIA; 339 stages IIIB/IIIC/IIID); 405 (79.9%) patients received AT (360/405 (88.9%) received anti-PD1 therapy; 45/405 (11.1%) received BRAF/MEK therapy). Physicians reported clinical guidelines (61.2%), treatment efficacy (37.5%), and ECOG performance status (31.6%) as drivers of AT prescription. Patient-level data confirmed that improving patient outcomes (79%) was the main reason for anti-PD1 prescription; expected limited treatment benefit (37%), patient refusal (36%), and toxicity concerns (30%) were reasons for not prescribing AT. In multivariable analyses stage IIIB/IIIC/IIID disease significantly increased the probability of receiving AT (odds ratio [OR] 1.74) and anti-PD1 therapy (OR 1.82); ECOG 2/3 and Medicaid/no insurance decreased the probability of AT receipt (OR 0.37 and 0.42, respectively) and anti-PD1 therapy (OR 0.41 and 0.42, respectively) among all patients and patients with stage IIIA disease. CONCLUSION: Most patients were given AT with a vast majority treated with an anti-PD1 therapy. Physician- and patient-level evidence confirmed the impact of disease substage on AT use, with stage IIIA patients, patients without adequate insurance coverage, and worse ECOG status having a lower probability of receiving AT.

Impact of COVID-19 Pandemic on Prescribing of Long-Acting Injectable Antipsychotics for Schizophrenia: Results from a United States Prescriber Survey.

Purpose: To describe changes due to the COVID-19 pandemic in the prescribing of long-acting antipsychotics (LAI) for schizophrenia, patient outcomes, and patient and healthcare provider (HCP) attitudes regarding COVID-19 vaccination in the United States (US). Methods: An anonymous online survey was administered to US-based LAI prescribers with a psychiatry specialty in May 2021. Information on prescriber and clinical practice characteristics, LAI prescribing, patient outcomes, and attitudes toward COVID-19 vaccination was collected and described. Results: Of the 401 LAI prescribers meeting survey criteria, 64.6% reported that LAI prescribing remained unchanged (increase: 19.2%, decrease: 14.0%). The majority did not switch patients from LAIs to oral antipsychotics (OAP; 63.3%) or to LAI formulations with lower frequency of administration (68.1%); most prescribers switched the same number of patients from OAPs to LAIs during the pandemic as in previous practice (65.1%). Half of LAI prescribers (50.1%) reported antipsychotic adherence as unchanged among most patients; 44.6% reported symptom control/relapse frequency as unchanged. Most prescribers believed their patients with schizophrenia should be prioritized for COVID-19 vaccination (74.1%) and encouraged all patients to obtain a COVID-19 vaccine (84.0%). However, 64.1% of prescribers reported hesitancy among some patients about vaccines' safety; 51.4% reported that some patients were willing to be vaccinated despite the hesitancy, 48.6% indicated that some patients perceived COVID-19 vaccines as safe, effective, and important. Conclusion: LAI prescribing and prescriber-reported antipsychotic adherence in patients with schizophrenia remained largely unchanged approximately one year after the start of COVID-19. Focused efforts to overcome patients' COVID-19 vaccine hesitancy are warranted.

Understanding the Health System Conditions Affecting the Use of Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia in Clinical Practice: A US Healthcare Provider Survey.

Purpose: To describe factors that enable the routine use of long-acting injectable antipsychotics (LAIs) for appropriate patients in the current clinical practice, including changes in LAI prescribing due to the COVID-19 pandemic and expectations for prescribing in 2021 in the United States (US). Methods: Frequent LAI prescribers recruited from a nationwide panel in 2020 completed an online survey regarding practice characteristics, perspectives on healthcare system conditions enabling routine use of LAIs, and prescribing patterns and changes in patterns during the COVID-19 pandemic. Results: Of 408 prescribers who completed the survey, 77.7% were physicians and 59.1% had ≥10 years of psychiatry practice. More than half of frequent prescribers (57.1%) reported treating >20% of their patients with schizophrenia with LAIs. The American Psychiatric Association (APA) guideline was followed by 64.0% of prescribers. Most prescribers identified poor adherence to antipsychotics as a circumstance when LAIs are recommended (94.9%) and patient/caregiver involvement in treatment decisions as a key factor impacting the decision to prescribe LAIs (97.3%). Most prescribers reported that LAI prescribing rates were unchanged in 2020 (59.8%). Similar proportions of prescribers expected no change (44.1%) or an increase (42.9%) in LAI prescribing rates in 2021. The number of patients followed, cost of treatment, and availability of staff to administer LAIs were the main driving factors identified by prescribers expecting an increase in LAI prescribing rates. Conclusion: LAIs were commonly recommended to patients with poor adherence, and patient/caregiver involvement was an important factor affecting prescribers' treatment decisions. LAI prescribing rates remained unchanged during the COVID-19 pandemic in 2020.

Assessment of the Impact of a Meningitis/Encephalitis Panel on Hospital Length of Stay: A Systematic Review and Meta-Analysis.

Meningitis and encephalitis are central nervous system infections with considerable morbidity and mortality. The BioFire® FilmArray® Meningitis/Encephalitis Panel (multiplex ME panel) can identify pathogens rapidly potentially aiding in targeted therapy and curtail antimicrobial exposure. This systematic review and meta-analysis synthesized the literature on the association between the multiplex ME panel and length of hospital stay (LOS), length of acyclovir therapy, and days with antibiotics. MEDLINE and EMBASE were searched. Only studies presenting novel data were retained. Random-effects meta-analyses were performed to assess the impact of the multiplex ME panel on outcomes. Of 169 retrieved publications, 13 met the criteria for inclusion. Patients tested with the multiplex ME panel had a reduction in the average LOS (mean difference [MD] [95% CI]: -1.20 days [-1.96, -0.44], n = 11 studies). Use of the multiplex ME panel was also associated with a reduction in the length of acyclovir therapy (MD [95% CI]: -1.14 days [-1.78, -0.50], n = 7 studies) and a nonsignificant reduction in the average number of days with antibiotics (MD [95% CI]: -1.01 days [-2.39, 0.37], n = 6 studies). The rapidity of pathogen identification contributes to an overall reduced LOS, reductions in the duration of empiric antiviral utilization, and a nonsignificant reduction in antibiotic therapy.

Real-world effectiveness after initiating fremanezumab treatment in US patients with episodic and chronic migraine or difficult-to-treat migraine.

BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings. METHODS: This retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway-targeted mAb [CGRP mAb]). RESULTS: Data were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were - 7.7 (77.0%) in EM patients, - 10.1 (68.7%) in CM patients, - 10.8 (80.6%) in the MO subgroup, - 9.9 (68.3%) in the MDD subgroup, - 9.5 (66.4%) in the GAD subgroup, and - 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively. CONCLUSIONS: In this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb).

Real-world effectiveness of fremanezumab in migraine patients initiating treatment in the United States: results from a retrospective chart study.

BACKGROUND: The efficacy and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine in adults, have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world data can further support those clinical trial data and demonstrate the full clinical benefits of fremanezumab. This chart review assessed the effectiveness of fremanezumab for improving clinical outcomes in adult patients with migraine treated according to real-world clinical practice. METHODS: This retrospective, panel-based, online physician chart review study used electronic case report forms with US physicians. Patient inclusion criteria were a physician diagnosis of migraine, fremanezumab treatment initiation at ≥ 18 years of age after US Food and Drug Administration approval, ≥ 1 dose of fremanezumab treatment, and ≥ 2 assessments of monthly migraine days (MMD; 1 within 30 days before treatment initiation and ≥ 1 after initiation). Changes from baseline in MMD, monthly headache days (MHD), and Migraine Disability Assessment (MIDAS) and 6-item Headache Impact Test (HIT-6) scores were assessed over 6 months. These endpoints were evaluated in the overall population and subgroups divided by dosing schedule and number of prior migraine preventive treatment failures. RESULTS: This study included data from 421 clinicians and 1003 patients. Mean age at fremanezumab initiation was 39.7 years, and most patients were female (75.8%). In the overall population, mean baseline MMD and MHD were 12.7 and 14.0, respectively. Mean (percent) reductions from baseline in MMD and MHD, respectively, were - 4.6 (36.2%) and - 4.7 (33.6%) at Month 1, - 6.7 (52.8%) and - 6.8 (48.6%) at Month 3, and - 9.2 (72.4%) and - 9.8 (70.0%) at Month 6. Mean (percent) reductions from baseline in MIDAS and HIT-6 scores also increased over the 6-month study period, from - 6.2 (21.6%) and - 8.4 (14.0%) at Month 1 to - 18.1 (63.1%) and - 16.2 (27.0%) at Month 6, respectively. Improvements in these outcomes over 6 months were observed across all evaluated subgroups. CONCLUSIONS: This real-world study demonstrated effectiveness of fremanezumab treatment for up to 6 months, irrespective of dosing regimen or number of prior migraine preventive treatment failures, reflecting ongoing, clinically meaningful improvements in patient outcomes.

Real-world outcomes of patients with locally advanced or metastatic epithelioid sarcoma.

BACKGROUND: Limited data are available on the real-world effectiveness and safety of systemic therapies for advanced (surgically unresectable and/or metastatic) epithelioid sarcoma (ES). METHODS: A retrospective medical records review was conducted in patients with advanced ES who were initiating first-line or ≥2 lines of systemic therapy (2000-2017) at 5 US cancer centers. The real-world overall response rate (rwORR), the duration of response (rwDOR), the disease control rate (rwDCR) (defined as stable disease for ≥32 weeks or any duration of response), and progression-free survival (rwPFS) were assessed by radiology reports. Overall survival (OS), rwDOR, and rwPFS were estimated from the time therapy was initiated using the Kaplan-Meier method. Serious adverse events were assessed. RESULTS: Of 74 patients (median age at diagnosis, 33 years; range, 10.6-76.3 years), 72% were male, and 85% had metastatic disease. The median number of lines of therapy was 2 (range, 1-7 lines of therapy), and 46 patients (62%) received ≥2 lines of systemic therapy. First-line regimens were usually anthracycline-based (54%) or gemcitabine-based (24%). For patients receiving first-line systemic therapy, the rwORR was 15%, the rwDCR was 20%, the median rwDOR was 3.3 months (95% CI, 2.1-5.2 months), the median rwPFS was 2.5 months (95% CI, 1.7, 6.9 months), and the median OS was 15.2 months (95% CI, 11.4-21.7 months). For those who received ≥2 lines of systemic therapy, the rwORR was 9%, the rwDCR was 20%, the median rwDOR was 4.5 months (95% CI, 0.7-5.6 months), and the median rwPFS was 6.0 months (95% CI, 3.2-7.4 months). Over one-half of patients (51.4%) experienced an adverse event, most frequently febrile neutropenia (14%), pain (10%), anemia, dyspnea, fever, thrombocytopenia, or transaminitis (5% each). CONCLUSIONS: Systemic therapies demonstrate limited efficacy in patients with advanced ES and have associated toxicities.

Survival and Clinical Outcomes with Telotristat Ethyl in Patients with Carcinoid Syndrome.

PURPOSE: The TELEACE study showed reductions in tumor size in patients with neuroendocrine tumors, receiving telotristat ethyl in US clinical practice. Here, we report progression-free survival, time to tumor progression, changes in carcinoid syndrome symptoms, and indictors of overall health. PATIENTS AND METHODS: This was a retrospective, single arm, pre-post medical chart review of patients with locally advanced or metastatic neuroendocrine tumors and documented carcinoid syndrome receiving telotristat ethyl for at least 6 months. Patients with poorly differentiated tumors, mixed tumor types or conflicting clinical trial enrollment were excluded. Descriptive statistics, Kaplan-Meier and chi-square tests were used to evaluate PFS, tumor progression, changes in symptoms, body weight and ECOG performance status before and after telotristat ethyl initiation. Subgroup analyses were conducted in patients with the same pre- and post-telotristat ethyl background treatment. RESULTS: Anonymized data for 200 patients were provided by 114 physicians; patients received telotristat ethyl for a median of 9 months. Median time to tumor progression was 39.8 months (IQR, 18.7-39.8); most had no tumor progression at 6 (92%) and 12 months (87%). Median progression-free survival was 23.7 months (17.8-39.8); most had progression-free survival at 6 (90%) and 12 months (80%). Results were consistent in the subgroup of 65 patients with the same pre/post background treatment. Nearly all patients had improved carcinoid syndrome symptoms, stable or improved weight and ECOG performance status. CONCLUSION: Patients showed improvements in clinical outcomes and indicators of overall health following treatment with telotristat ethyl in this exploratory pilot study, consistent with previously observed reductions in tumor size.