See Appendix for individual names.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 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg 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, nabpaclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months 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 months 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.
Risk-sharing agreements between pharmaceutical companies and payers stand out as a recent practice, the use of which has been increasing in the case of innovative medicines, particularly in the field of oncology, which aims to ensure better budgetary control and a lower risk of spending on medicinal products without full evidence of clinical benefit.In this article, the authors discuss the types of existing agreements, as well as those used in Portugal, their advantages, disadvantages and future challenges of implementation, as well as their potential role in access to therapeutic innovation, namely medicines for cancer treatment. For this purpose, a nonsystematic review of indexed and nonconventional literature was carried out.There is a tendency for the risk-sharing agreements established between payers and pharmaceutical companies to include a component of monitoring the use of medicines and outcomes measurement, involving real life data collection. Portugal is no exception and, although most agreements are still financial in nature, there is already a strong desire for other agreements, in particular clinical outcomes based.It is concluded that there is not yet a gold standard methodology in relation to the type of agreements to be practiced. Moreover, its opportunity cost, including the cost of implementation, remains to be scrutinised. However, regardless of the type of agreement, the advantages of adopting these agreements are well known, inevitably related with challenges of implementation. The need for an infrastructure to support information sharing is undisputed and urgent.The future of therapeutic innovation and increased pressure on health budgets will require alternative, more flexible models, personalized reimbursement models that allow alignment of medicines prices with the value they deliver in treating the several diseases.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Background:The "Quality of Recovery 15" questionnaire is used for the study of quality recovery after anesthesia. The aim of this study was to validate the Portuguese version of "Quality of Recovery 15" questionnaire. Material and Methods:After study approval by the institutional ethics committee, an observational and cohort prospective study was conducted on patients scheduled for elective surgery from June to August 2013. The "Quality of Recovery 15" questionnaire was translated in accordance with available guidelines. The "Quality of Recovery 15" Portuguese version was used before surgery (T0) and 24h postoperatively (T1) on 170 patients. Patients who were unable to give informed consent or had cognitive impairment were excluded. Poor quality of recovery was defined for "Quality of Recovery 15" score at T1 lower than the mean "Quality of Recovery 15" score minus 1 standard deviation. Reliability and observer disagreement was assessed using interclass correlation. Non-parametric tests were used for comparisons.Results: There was a negative correlation between "Quality of Recovery 15" score and time spent in the postanesthesia care (ρ = −0.264, p = 0.004) and length of hospital stay (ρ = −0.274, p = 0.004). Thirty-two patients (19%) had poor quality of recovery. Patients with poor quality of recovery had more frequently diabetes mellitus and hypertension and they were taking antidepressants drugs more frequently. Patients with poor quality of recovery were more frequently submitted to combined anesthesia and less frequently to general anesthesia and locoregional anesthesia (p = 0.008). The questionnaire had a good internal consistency and test-retest reliability was good. Discussion: The Portuguese version of the "Quality of Recovery 15" showed a good correlation with the original. Conclusion:This questionnaire appears to be an accurate and reliable assessment for quality of recovery.
Background: Our understanding of the interaction between the host immune system and cancer has evolved rapidly over the previous 10 years due to the clinical success induced by checkpoint inhibition. Previous immunologic work can now be realized in combination strategies. Modified Vaccinia Ankara (MVA) offers significant opportunities due to its natural induction of innate and adaptive immunity, large payload, and excellent safety profile. Methods: MVA vectors were administered subcutaneously (SC), intravenously (IV) or intratumorally (IT) into tumor-bearing mice. Cytokine secretion profile in serum was assessed by Luminex analysis. NK and T cell infiltration and activation in various organs and cytolytic activity against target cells were determined by flow cytometrybased assays. PD-1 immune checkpoint blockade (ICB), low dose cyclophosphamide, tumor-targeting Abs or 15 Gy radiotherapy were administered along with IV MVA. Results: Recombinant MVA (rMVA) in which tumor antigens and costimulatory molecules are encoded can be customized for maximal effect by route of administration. rMVA administered intravenously (IV) causes superior induction of antigen specific T cells, cytokines and NK cells than previously seen with subcutaneous or intramuscular routes. Encoding CD40L in addition amplifies the effects and efficacy improves in relevant models. This is dependent on T cells and NK cells, indicating a potential solution to one tumor-resistance mechanism, MHC loss and/or mutation. Furthermore, the combination of rMVA with tumor targeting antibodies, checkpoint inhibition, radiotherapy or chemotherapy often showed additional synergistic therapeutic effects. Administration of MVA alone intratumorally (IT) causes innate immune activation through toll like receptors (TLRs) as well as the cGAS / STING pathway. Recombinant antigen encoding rMVA improves systemic and local antigen-specific T cell responses. These effects can be bolstered by encoding certain costimulatory molecules. Conclusions: IV and IT recombinant MVA may offer off the shelf solutions to resolve many of the host -tumor immunity interactions that result in lack of efficacy of checkpoint inhibition alone in most patients. Bavarian Nordic plans to initiate clinical trials with existing agents in 2019 applied IV and IT and will create novel constructs to maximize clinical effect, planned to initiate in 2020 and beyond. Legal entity responsible for the study: Bavarian Nordic, Inc.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.