Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

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

Chapter 2. Hà Nội: the villages, the heart of social and patrimonial life

Unlike large Southeast Asian cities with primary trade and port functions, Hà Nội was founded in the Upper Delta, along the Red River, as the administrative centre of the feudal empire of Vietnam, after more than a thousand years of Chinese colonisation. The city at the head of an agrarian and, to a lesser degree, merchant empire, Vietnam’s capital had developed very close ties with its hinterland, particularly through the Quarter of 36 Streets and Corporations. In keeping with the Chinese mo..

Chapter 1. Hà Nội between the ‘waters’

Originally made up of urban villages dotted with ponds and pools, the Old Quarter of 36 Streets and Corporations, and a citadel where water flowed through a moat linked to the hydraulic system, the city of Hà Nội has spread out over its fringes, integrating very populous and multi-activity villages and lake replacement basins in the surrounding area. It has been erected ‘between’ the waters and ‘on’ the waters at very variable rhythms in an environment very prone to flooding and threatened by..

Produits laitiers à base de lait de chamelle, les nouvelles possibilités au Turkménistan

International audienceINTRODUCTION:The aim of this study was to assess the differential laxity after reconstruction of the anterior cruciate ligament (ACL) by the TLS® technique using a single tendon, the semitendinosus in four-strand graft, compared with the hamstring technique which uses both the gracilis and semitendinosus. We hypothesised that this surgical technique would provide post-surgical differential laxity measurements at least as good as those of the hamstring technique.MATERIALS AND METHODS:We carried out a prospective monocentric study on patients undergoing unilateral anterior cruciate ligament repair between December 2014 and June 2016. All patients were followed up for at least 12 months. The series compares 61 patients operated on using the TLS® technique by the same surgeon, with 33 patients operated on using the hamstring technique by a second surgeon. The main objective of the study was to compare the post-operative differential laxity, measured using the KT1000, between the two techniques.RESULTS:There was no significant difference in the patients' epidemiological characteristics and pre-operative scores between the two groups. Average pre-operative differential laxity was 6.5 mm ± 2.1 (min 3; max 12) in the TLS group and 6.4 mm ± 2.0 (min 0; max 11) in the hamstring group, with no statistically significant difference. The average post-operative difference in laxity was - 0.1 mm ± 1.9 (min - 5; max 4) in the TLS group and 0.3 mm ± 2.0 (min - 7; max 5) in the hamstring group. Again, no significant difference was observed between groups.DISCUSSION:This study demonstrates a level of post-operative differential laxity control using TLS comparable with that of the ACL reconstruction technique using a hamstring graft with preserved tibial insertio

Hà Nội, a Metropolis in the Making

Built on 'the bend in the Red River', Hà Nội is among Southeast Asia's most ancient capitals. Over the centuries, it took shape in part from a dense substratum of villages. With the economic liberalisation of the 1980s, it encountered several obstacles to its expansion: absence of a real land market, high population densities, the government's food self-suffciency policy that limits expropriations of land and the water management constraints of this very vulnerable delta. Since the beginning of the new millennium, the change in speed brought about by the state and by property developers in the construction and urban planning of the province-capital poses the problem of integration of in situ urbanised villages, the importance of preserving a green belt around Hà Nội and the necessity of protection from flooding. The harmonious fusion of city and countryside, which has always constituted the Red River Delta's defining feature, appears to be in jeopardy. Working from a rich body of maps and field studies, this collective work reveals how this grass-roots urbanisation encounters 'top-down' urbanisation, or metropolisation. By combining a variety of disciplinary approaches on several different scales, through a study of spatial issues and social dynamics, this atlas not only enables the reader to gauge the impact of major projects on the lives of villages integrated into the city's fabric but also to re-establish the peri-urban village stratum as a fully-fledged actor in the diversity of this emerging metropolis

ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): Final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial

Background: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. Patients and methods: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. Results: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P=0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). Conclusion: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved