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

Resenha de “Sistemas agrários em Paraíba do Sul (1850-1920) – Um estudo de relações não-capitalistas de produção”, de João Luís Fragoso

Review of an unpublished master’s dissertation by one of Brazil’s leading historians. Digital access to it, only recently made available, has revealed an innovative interpretation on one of Brazil’s economic history central questions: when, exactly, and why was there a crisis in coffee production at the Paraíba valley in the 19th century? The author relates the widely used slashand burn technique to factor endowments (land abundance and labor scarcity), thus presenting a new explanation to the valley’s and Brazil’s coffee production history, hitherto widely ignored.Resenha da dissertação de mestrado de um dos mais importantes historiadores brasileiros, até hoje não publicada, cuja defesa completa 40 anos em 2023. A recente digitalização da obra revela uma interpretação inovadora sobre a decadência produtiva do Vale do Paraíba no fim do século XIX. O autor explica o sistema de plantio extensivo na região, com utilização de queimadas, como uma solução racional para o problema da oferta relativa de fatores à época: abundância de terras e escassez de trabalhadores. Cria, assim, uma terceira via interpretativa para a história do Vale e a crise do café na região, até hoje ignorada

Implant-supported titanium framework: Photoelastic analysis before and after spark erosion procedure

Aim: This study used a photoelastic analysis to evaluate the passive fit of titanium cast laser welding frameworks before and after spark erosion procedure. Methods: A stainless steel cast was used in order to reproduce a human mandible. Five Multi-Unit abutment analogs were attached to this cast and 6 frameworks were produced in commercial pure titanium. The cast was molded and a photoelastic matrix was produced incorporating 5 dental implants with Multi-Unit abutments. All samples were subjected to a laser welding. The precision of adjustments within a range of 0.5 μm was evaluated under microscope observation. The best fitted framework was selected and subjected to a photoelastic analysis (Group I). The tightening of the screws was in 3 predetermined sequences (1,2,3,4,5/ 5,4,3,2,1/ 3,2,4,1,5). Then the same framework was subjected to a refinement by spark erosion technique (Group II) and evaluated by photoelastic analysis. Results: The sequence (3,2,4,1,5) achieved better results in both groups. A larger number of fringes were observed around the median implants in all sequences in both groups. Conclusions : The titanium cast laser welded frameworks processes associated with spark erosion procedure improves significantly the marginal framework adaptation and is effective for its passive fit