Introduction Erenumab, a first-in-class monoclonal antibody targeting the calcitonin gene-related peptide pathway, was approved by the US Food and Drug Administration in 2018 for the prevention of migraine in adults. There is limited data available on its impact in real-world settings. The study aim was to characterize the real-world treatment profiles, clinical outcomes, and healthcare resource utilization of patients prescribed erenumab from select major US headache centers. Methods A retrospective chart review of patients with migraine treated with erenumab for at least 3 months across five major headache centers was conducted. Data was collected from patient charts between April 2019 and April 2020 and included patient and clinical characteristics, migraine medication use, and outpatient visits. The date of the first prescription fill of erenumab was defined as the index date. The baseline period comprised the 3 months prior to the index date and the study period comprised the at least 3 months on erenumab treatment. Results Data from a total of 1034 patients with chronic migraine with a mean of 9.3 months of erenumab treatment were analyzed. Patients were on average 48 years old, 86% were female, and 79% were white. Patients had a mean of 5 preventive treatment failures prior to erenumab initiation. Patients used a mean of 2 preventive treatments (excluding erenumab) and 2 acute treatments during baseline and study periods. Among patients with effectiveness data, 45% of patients had improvement in physician-reported migraine severity and 35% experienced at least 50% reduction in mean headache/migraine days per month. The average number of monthly outpatient visits was 0.43 and 0.30 before and after erenumab initiation, respectively. Conclusion In this predominantly refractory chronic migraine population treated in select headache centers, patients had fewer headache/migraine days per month and outpatient visits after initiating erenumab. However, patients largely continued to be managed via a polypharmacy approach after erenumab initiation.

TPS1124 Background: Immunotherapy has shown therapeutic promise in several cancers, including breast cancer. Monotherapy with anti-PD-1/anti-PD-L1 antibodies has demonstrated durable responses in patients with metastatic triple-negative breast cancer (mTNBC) (Nanda et al, JCO 2016) and metastatic estrogen receptor-positive (mER+)/HER2-negative breast cancer (Rugo et al, SABCS 2015). Furthermore, response rates have been increased with combination approaches with chemotherapy (Adams et al, ASCO 2016). Based on these results, we seek to study the anti-tumor efficacy and safety of pembrolizumab (anti-PD-1 antibody) and nab-paclitaxel, the impact of therapy on the tumor microenvironment, and predictive markers of response. Methods: This is an ongoing single-arm open-label multi-cohort phase II study of pembrolizumab and nab-paclitaxel in patients treated with ≤2 prior lines of therapy for metastatic HER2-negative breast cancer (n = 50) (ClinicalTrials.gov: NCT02752685). Thirty patients with mTNBC and 20 patients with mER+/HER2-negative breast cancer will be enrolled. Enrollment of patients with metaplastic breast cancer is encouraged. Patients will receive pembrolizumab 200 mg IV on day 1 plus nab-paclitaxel 100 mg/m2 IV on day 1 and 8 (21-day cycle). Prior taxane therapy given > 3 months before cycle 1 is allowed. Primary objective is treatment efficacy, as determined by overall response rate (RECIST 1.1). Secondary objectives include safety, progression-free survival, overall survival, and duration of response. Serial tumor biopsies will be performed to assess changes in the tumor microenvironment from baseline with chemotherapy alone (cycle 1) and then with chemoimmunotherapy (cycle 2 and subsequent cycles). Mutational and neoantigen load, TILs by histopathological assessment, TCR by immunosequencing, and immune gene profiles in tumors will be evaluated. PD-L1 expression in tumor tissue is not required for enrollment but will be assessed as a predictive marker. The potential role of the gut microbiome in modulating the immune response will also be evaluated by 16S rRNA. An initial safety run-in with 12 subjects has been completed with no unexpected toxicity. Clinical trial information: NCT02752685.

Objective.-To evaluate the pharmacokinetics, safety, and tolerability of a single 50-mg oral dose of diclofenac potassium for oral solution (OS) in a pediatric cohort with a diagnosis of episodic migraine; the 3-month safety trial following an outpatient dosing period was also evaluated. Background.-Children and adolescents often experience migraine pain that is poorly controlled, which may affect their emotional and psychological well-being. Diclofenac potassium for OS is approved for the treatment of migraine with aura (MWA) or migraine without aura (MWoA) in adults 18 years of age or older. It is formulated in a soluble buffered powder that provides more rapid absorption than the tablet formulations of diclofenac potassium. In a randomized, double-blind, crossover trial, more adult patients were pain-free at 2 hours post-dose following treatment with diclofenac potassium for OS than those who received the diclofenac tablet formulation or placebo. Methods.-This was a Phase 4 open-label study that took place at 2 US sites. Participants 12-17 years of age with a diagnosis of episodic MWA or MWoA for ≥3 months and ≤14 headaches per month were enrolled in the study. Participants received one 50-mg dose of diclofenac potassium for OS under fasted conditions on day 1. Blood samples were collected for PK analysis within 15 minutes pre-dose and at 5, 10, 15, 20, 30, 40, and 60 minutes post-dose, and at 2, 4, and 6 hours postdose. Safety evaluations were performed after the initial dose and at the end of study on day 90; adverse events were monitored throughout the study. After completing the PK assessments, participants were given a 3-month supply (27 packets) of diclofenac potassium for OS (50-mg doses) for their migraine attacks. Participants were advised to take diclofenac potassium for OS at the onset of a migraine. They were told to take no more than 2 doses daily and not to use it more than 3 days/week. Results.-Twenty-five participants completed the study; 84% were females and 96% were white or Caucasian, with a mean age of 15.5 years and a mean weight of 63.1 kg. Diclofenac was rapidly absorbed with a median time to maximum concentration of 15 minutes and a mean peak plasma concentration of 1412 (±846.2) ng/mL. Diclofenac had a half-life of 66.8 (±9.2) minutes. The mean area under the concentration-time curve from zero to the last measurable time point was 82,920.0 (±25,327.6) minutes × ng/mL, and the mean area under the concentration-time curve from time zero to infinity was 84,388.8 (±25,993.6) minutes × ng/mL. Participants took the study drug an average of 10 times over 79 days, with an overall total drug exposure of 506 mg. No deaths or discontinuations due to an AE were reported during the study. The most frequently reported treatment emergent adverse events were arthralgia and motion sickness, each of which occurred in 2 (8%) of the participants. Conclusions.-Diclofenac potassium for OS exhibited a favorable pharmacokinetic and safety profile in 12-to 17-year-old patients with a diagnosis of episodic MWA ...