Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of-opportunity trial.

Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers. In a xenograft model of intracranial breast cancer, SG inhibited tumor growth and increased mouse survival. We conducted a prospective window-of-opportunity trial (NCT03995706) at the University of Texas Health Science Center at San Antonio to examine the intra-tumoral concentrations and intracranial activity of SG in patients undergoing craniotomy for breast cancer with brain metastases (BCBM) or recurrent glioblastoma (rGBM). We enrolled 25 patients aged ≥18 years diagnosed with BCBM and rGBM to receive a single intravenous dose of SG at 10 mg/kg given one day before resection and continued on days 1 and 8 of 21-day cycles following recovery. The PFS was 8 months and 2 months for BCBM and rGBM cohorts, respectively. The OS was 35.2 months and 9.5 months, respectively. Grade≥3 AE included neutropenia (28%), hypokalemia (8%), seizure (8%), thromboembolic event (8%), urinary tract infection (8%) and muscle weakness of the lower limb (8%). In post-surgical tissue, the median total SN-38 was 249.8 ng/g for BCBM and 104.5 ng/g for rGBM, thus fulfilling the primary endpoint. Biomarker analysis suggests delivery of payload by direct release at target site and that hypoxic changes do not drive indirect release. Secondary endpoint of OS was 35.2 months for the BCBM cohort and 9.5 months for rGBM. Non-planned exploratory endpoint of ORR was 38% for BCBM and 29%, respectively. Exploratory endpoint of Trop-2 expression was observed in 100% of BCBM and 78% of rGBM tumors. In conclusion, SG was found to be well tolerated with adequate penetration into intracranial tumors and promising preliminary activity within the CNS. Trial Registration: Trial (NCT03995706) enrolled at Clinical Trials.gov as Neuro/Sacituzumab Govitecan/Breast Brain Metastasis/Glioblastoma/Ph 0: https://clinicaltrials.gov/study/NCT03995706?cond=NCT03995706 .

Outcomes in chronic lymphocytic leukemia patients on novel agents in the US Veterans Health Administration System.

The US veteran population has a high proportion of chronic lymphocytic leukemia (CLL) risk factors. Using the Veterans Health Administration (VHA) population, we conducted a retrospective chart review of 1205 CLL patients who initiated treatment with a novel oral agent. For 1L ibrutinib, 33% (n = 107) discontinued therapy during the study, of which 64% discontinued due to adverse events (AEs). For relapsed/refractory (R/R) ibrutinib, 35% (n = 262) discontinued therapy, of which 63% discontinued due to AEs. For R/R venetoclax, 31% (n = 27) discontinued therapy, of which 41% were due to AEs. For idelalisib, 84% (n = 41) discontinued therapy, of which 54% were due to AEs. This real-world study suggests that AEs play an important role in dose reductions and discontinuations; however, physician inexperience in using these drugs when they were first introduced could be part of what is leading to these negative outcomes.

Integrative Approaches to Managing Myeloproliferative Neoplasms: the Role of Nutrition, Exercise, and Psychological Interventions.

PURPOSE OF REVIEW: Myeloproliferative neoplasms (MPNs) have a high symptom burden that affects functional status, emotional well-being, and quality of life for patients. Symptom control continues to be a challenging therapeutic goal despite available pharmacologic interventions. The goal of this review is to detail recent efforts that have focused on non-pharmacologic interventions, such as wholistic or integrative medicine, as an adjunctive method to alter symptom burden in this population. RECENT FINDINGS: We discuss the ongoing physical, nutritional, and psychological interventional efforts which represent promising non-traditional interventions to date to help reduce symptom in MPN patients. In this article, we highlight the early promising data and importance of these various non-pharmacological interventions to dampen symptom burden and reduce disease-related inflammation. Nonpharmacologic interventions represent promising therapeutic strategies to alter traditional MPN treatment paradigms and improve MPN patient care.