Virtual Molecular and Precision Medicine Clinic to Improve Access to Clinical Trials for Patients With Metastatic Breast Cancer: An Academic/Community Collaboration.

PURPOSE: There is a demand for improved care delivery surrounding genomic testing and clinical trial enrollment among patients with metastatic breast cancer (MBC). We sought to improve the current process via real-time informal consultation and prescreening assessment for patients with MBC treated by community and academic medical oncologists by implementing a virtual molecular and precision medicine (vMAP) clinic. METHODS: The vMAP program used a virtual referral system directed to a multidisciplinary team with precision medicine expertise. Providers contacted vMAP regarding patients with MBC, and on receipt of referral, the vMAP team engaged in discussion to identify if further diagnostics were needed (including genomic testing) and to identify potential clinical trials or standard treatment options. Recommendations were then sent to the referring provider within 72 hours. Pre-/postsurveys were issued to network physicians to assess for barriers, clinical trial access, and vMAP referral experience. Program implementation was evaluated with the Squire 2.0 reporting guidelines for quality improvement in health care as a framework. RESULTS: Eighty-one cases from 22 providers were referred to vMAP over a 26-month period. The average response time to the referring provider with a finalized recommendation was 1.90 ± 1.82 days. A total of 86.4% of cases had clinical trial options on vMAP prescreen, with 40.7% initiating formal screening assessments and 27 patients (33.3%) ultimately enrolling on trials. On resurvey, 92% of survey responses across community oncology referring providers said that they were very likely to use vMAP again. CONCLUSION: In the initial 2-year period, vMAP demonstrated an efficient means to offer real-time interpretation of genomic testing and identification of clinical trials for patients with MBC, with effective clinical trial enrollment and high rates of referring provider satisfaction.

The synthesis and biological evaluation of quinolyl-piperazinyl piperidines as potent serotonin 5-HT1A antagonists.

As part of an effort to identify 5-HT(1A) antagonists that did not possess typical arylalkylamine or keto/amido-alkyl aryl piperazine scaffolds, prototype compound 10a was identified from earlier work in a combined 5-HT(1A) antagonist/SSRI program. This quinolyl-piperazinyl piperidine analogue displayed potent, selective 5-HT(1A) antagonism but suffered from poor oxidative metabolic stability, resulting in low exposure following oral administration. SAR studies, driven primarily by in vitro liver microsomal stability assessment, identified compound 10b, which displayed improved oral bioavailability and lower intrinsic clearance. Further changes to the scaffold (e.g., 10r) resulted in a loss in potency. Compound 10b displayed cognitive enhancing effects in a number of animal models of learning and memory, enhanced the antidepressant-like effects of the SSRI fluoxetine, and reversed the sexual dysfunction induced by chronic fluoxetine treatment.