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

Seismo-Lineaments in Egypt: Analysis and Implications for Active Tectonic Structures and Earthquake Magnitudes

Quiescent faults may be capable of creating catastrophic earthquakes in locations with moderate and/or low seismic activity, such as Egypt. This study combines structural, remote sensing (RS), geophysical, and seismic activity data to examine and analyze the relationship between tectonic structures and seismotectonic activity in Egypt. In a new seismo-lineaments map of Egypt, tectonic lineaments of the Egyptian mainland were delineated and classified. The database contains 8000 lineaments that were divided into distinct geographical zones using statistical analysis and general features. Delineated lineaments were integrated with digitized geological and geophysical surface and subsurface faults and geographic information systems (GIS) processing techniques were applied to produce 4249 faults. The spatial distribution of seismic activity was determined to extract 1968 competent faults out of 4249 capable faults (i.e., greater than 10 km and suitably orientated concerning the existing stress field). Maximum expected magnitudes (Mmax) were calculated for distinct seismogenic locations in Egypt, taking into account the nature of the regional rupture. At the national scale, empirical scaling relations between fault lengths and earthquake magnitude were employed for all mapped faults in Egypt. The findings concerning the faults were highly consistent with traditional geological information. The results suggest that our technique for estimating the highest predicted magnitudes produces similar values and might be used to evaluate Egypt’s possible future seismic hazard. The results were compared to seismic databases. The similarity of our results with those reported in the catalogs lends confidence to the proposed scheme