Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Low baseline proBNP associated with increased risk of intraoperative hypotension during spinal anaesthesia for cesarean delivery

BACKGROUND AND OBJECTIVES: Brain natriuretic peptide (BNP) has a role in the regulation of body fluid volume and blood pressure (BP). BNP remains within a normal range during spinal anaesthesia (SA) in patients undergoing cesarean delivery. However, the effect of BNP on changes in BP during the perioperative period has not been evaluated. We aimed to investigate the effect of preoperative serum BNP on the risk of hypotension during cesarean delivery with SA. DESIGN AND SETTING: Patients were randomly selected among the patient group who were attending routine clinic visits for pregnancy monitoring. All had a healthy pregnancy and no other acute or chronic disease by their obstetrician. The study design was cross-sectional. PATIENTS AND METHODS: Patients who had uncomplicated pregnancy process and no known medical disease were selected consecutively during their last outpatient clinical examination. Baseline BP was recorded before SA. Simultaneously, blood samples were drawn for routine biochemistry and BNP. BP, SaO(2), and electro-cardiography were monitored during surgery. Intraoperative hypotension (IOH) was defined as >= 25% decrease in mean arterial pressure (MAP) at the 5th minute of SA. RESULTS: In 41 term pregnant women, 18 of the 41 patients (43.9%) fulfilled the criteria for IOH, while 23 (56.1%) showed a decrease 13.1 (11.3%) and were classified as normotensive. Baseline BNP was significantly lower in patients with IOH compared with normotensive patients 45.7 (26.9) vs. 70.2 (40.5); P=. 05. Baseline BNP had no significant correlation MAP at any time point. Age, body mass index, hemoglobin, baseline MAP and heart rate were not different between patients with and without IOH. CONCLUSION: Those findings suggest that higher baseline BNP levels might have a protective role in development of hypotension in healthy term pregnant women during SA for cesarean delivery