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

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

A New Gall-Forming Species of \u3ci\u3eAnguina\u3c/i\u3e Scopoli, 1777 (Nemata: Anguinidae) on Bluegrass, \u3ci\u3ePoa annua\u3c/i\u3e L., from the Coast of California

Anguina pacificae n. sp. is described and illustrated from stem galls on bluegrass, Poa annua L., from golf courses along coastal California. The females are characterized by constrictions in the anterior and posterior connections of the isthmus with the respective parts of the esophagus, the long multicellular columella, and the sharply pointed tail tip. Males are dorsally curved after death; body width is increased markedly after 13 annuli in both sexes, and the tail is conical and with an acute terminus

Las actitudes ambientales de los estudiantes de la maestría en desarrollo educativo: (generación 2004-2006)

Maestría en Desarrollo Educativ

Description of \u3ci\u3eGracilacus harnicaudata\u3c/i\u3e sp. n. (Nemata : Criconematidae) with Biological and Histopathological Observations

Obese criconematid females and larvae forming colonies were detected under the root cortex attached to the vascular cylinder of redwood roots, Sequoia sempervirens (D. Don) Endl. These specimens have been determined to represent a new species of Criconematidae, Grmilacus lzanzicaudata sp. n. Mature females are obese at midbody but posteriorly the body is constricted and hooked shaped with a rounded tail terminus. Annuli are conspicuous only anteriorly and posteriorly. The cephalic region has four submedian lobes and a circular oral disc. The vulval-lips protrude and the lateral field is marked with four lines. Eggs are partially embedded in a mucoid-like substance. There are giant nutritive cells formed in the parenchyma tissue of the vascular cylinder associated with the nematode colonies. These cells have dense cytoplasm with enlarged nuclei. Starch granules were found inside of these abnormal cells. French language title: Description de Gracilacus hamicaudata sp. n. (Nemata : Cnconenzatidae) et observations sur la biologie et l’histopathologie de cette espèce French language abstract: Des femelles renflées et des juvéniles d’un Criconematide ont été observés, assemblés en colonies, sous le cortex radiculaire et attachés au cylindre central de racines de Sequoia sempervirens (D. Don) Endl. Ils appartiennenàt une nouvelle espèce, Gracilacus hamicaudata sp. n. Les femelles matures sont renflées dans leur partie centrale, mais la partie postérieudreu corps est rétrécie et en forme de crochet, l’extrémité caudale étant arrondie. L‘annélation cuticulaire n’est visible que vers l\u27avant et l’arrière de la femelle. La région céphalique comporte quatre lobes submédians eut n disque oral circulaire. Les lèvres vulvaires sont en relief et le champ latéral comporte quatre lignes. Les oeufs sont en partie entourés par une substance mucoïde. Des cellules nutritives géantes sont formées dans le tissu parenchymatique du cylindre central, en association avec la présence des colonies du nématode. Ces cellules présentent un cytoplasme dense et des noyaux agrandis. Des granules d’amidon ont étě observés à l’intérieur de ces cellules modifiées