Safety profile of pertuzumab with trastuzumab and docetaxel in patients from asia with human epidermal growth factor receptor 2-positive metastatic breast cancer: Results from the phase III trial CLEOPATRA
Swain S.M.,Washington Cancer Institute |
Im Y.-H.,Sungkyunkwan University |
Im S.-A.,Seoul National University |
Chan V.,Veterans Memorial Medical Center |
And 5 more authors.
Oncologist | Year: 2014
Introduction. We report detailed safety analyses by geographic region from the phase III study CLEOPATRA with pertuzumab, trastuzumab, and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive first-line metastatic breast cancer. Patients and Methods. Patients received pertuzumab/placebo at 840 mg in cycle 1 and 420 mg in subsequent cycles, and trastuzumab at 8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles; docetaxel was initiated at 75 mg/m2. All study drugs were given intravenously, 3 times weekly. Results. Docetaxel dose reductions below 75 mg/m2 were more common in patients from Asia (47.0%) than other regions (13.4%); docetaxel dose escalations to 100 mg/m2 were less frequent in Asia (2.4%) than other regions (18.7%). Rates of edema (26.1% and 5.4% for Asia and other regions, respectively), myalgia (42.3%, 14.7%), nail disorder (39.9%, 15.1%), febrile neutropenia (18.6%, 7.1%), upper respiratory tract infection (25.7%, 10.2%), decreased appetite (47.0%, 19.1%), and rash (44.3%, 22.0%) were at least twice as high in Asia as in other regions. Adverse events did not result in a reduction in the median number of study treatment cycles administered in patients from Asia. Efficacy analyses per region showed hazard ratios similar to those of the whole intention-to-treat (ITT) population for progression-free survival (ITT: 0.63; Asia: 0.68; other regions: 0.61) and overall survival (ITT: 0.66; Asia: 0.64; other regions: 0.66). Conclusion. Despite a higher proportion of docetaxel dose reductions in patients from Asia, survival benefits were comparable between regions. The benefit-risk profile of pertuzumab, trastuzumab, and docetaxel supports this regimen as the first-line therapy for patients with HER2-positive metastatic breast cancer from all geographic regions. © Alpha Med Press 2014.
Vogelmeier C.,Universitatsklinikum Giessen und Marburg |
Aquino T.O.,Veterans Memorial Medical Center |
O'Brien C.D.,Astrazeneca |
Perrett J.,Astrazeneca |
COPD: Journal of Chronic Obstructive Pulmonary Disease | Year: 2012
AZD9668 is a fully reversible, selective, oral inhibitor of neutrophil elastase, a protease implicated in chronic obstructive pulmonary disease (COPD). Efficacy, safety and tolerability of AZD9668 (5, 20 and 60 mg bid) were compared with placebo in a randomised, double-blind, placebo-controlled, 12-week, Phase IIb trial (NCT00949975: approved by an Investigational Review Board), in patients with symptomatic COPD receiving maintenance tiotropium. The primary endpoint was pre-bronchodilator forced expiratory volume in 1 second (FEV1). Secondary endpoints included forced vital capacity and inspiratory capacity, peak expiratory flow, Breathlessness, Cough and Sputum Scale score, exercise capacity, quality of life (QoL), exacerbation assessments, safety and pharmacokinetics. Exploratory endpoints included inflammatory and tissue degradation biomarkers. A total of 838 patients were randomised to AZD9668 5 mg bid (212 patients), 20 mg bid (206 patients), 60 mg bid (202 patients) or placebo (218 patients). AZD9668 showed no effect on lung function, respiratory signs and symptoms, QoL or biomarkers. At end of treatment, the change in mean pre-bronchodilator FEV1 for AZD9668 60 mg bid compared with placebo was 0.00L (95% confidence interval: -0.05, 0.04; p = 0.873). Overall, AZD9668 was well tolerated; the numbers of patients with adverse events (AEs), serious AEs and AEs leading to discontinuation were similar in each of the four study groups. AZD9668 60 mg bid showed no clinical benefit and no effect on biomarkers of inflammation or tissue degradation when added to tiotropium in patients with COPD. These results raise important questions for future investigation of anti-inflammatory and disease-modifying agents in patients with COPD. © 2012 Informa Healthcare USA, Inc.
Yang J.C.H.,National Taiwan University Hospital |
Wu Y.-L.,Guangdong Lung Cancer Institute |
Chan V.,Veterans Memorial Medical Center |
Kurnianda J.,Sardjito Hospital |
And 6 more authors.
Lung Cancer | Year: 2014
Objectives: Epidermal growth factor receptor (EGFR) mutation testing is standard practice after lung adenocarcinoma diagnosis, and provision of high-quality tumor tissue is ideal. However, there are knowledge gaps regarding the utility of cytology or low tumor content histology samples to establish EGFR mutation status, particularly with regard to the proportion of testing performed using these sample types, and the lack of an established link with efficacy of treatment. Methods: The randomized phase III Iressa Pan-ASia Study (IPASS; ClinicalTrials.gov identifier NCT00322452) of first-line gefitinib versus chemotherapy analyzed samples meeting preplanned specifications (n=437 evaluable for EGFR mutation; n=. 261 mutation-positive). This supplementary analysis assessed tumor content and mutation status of histology (n=99) and cytology samples (n=116) which were previously unanalyzed due to sample quality, type, and tumor content (<100 cells). Objective response rate (ORR) and change in tumor size with gefitinib treatment were assessed. Results: EGFR mutation testing was successful in 80% and 19% of previously unanalyzed histology and cytology samples, respectively. Mutations were detected in 54 tumors previously described as mutation-unknown (histology, n=. 45; cytology, n=. 9). ORRs in mutation-positive cytology (83%) and histology (74%) subgroups were consistent with previous analyses (71%). Tumor size decrease was consistent across previously analyzed and unanalyzed samples (all mutation subgroups), with less consistency across ORRs in mutation-negative cytology (16%) and histology (25%) subgroups versus the previous analysis (1%). Conclusions: Histology samples with low tumor content and cytology samples can be used for EGFR mutation testing; patients whose mutation status was confirmed using these sample types achieved a response to treatment consistent with those confirmed using high-quality histology samples. Better sample quantity/quality can potentially reduce false-negative results. © 2013 The Authors.
Van Olmen J.,Institute of Tropical Medicine |
Ku G.M.,Institute of Tropical Medicine |
Ku G.M.,Veterans Memorial Medical Center |
Bermejo R.,Institute of Tropical Medicine |
And 3 more authors.
Globalization and Health | Year: 2011
Background: The growing caseload caused by patients with chronic life-long conditions leads to increased needs for health care providers and rising costs of health services, resulting in a heavy burden on health systems, populations and individuals. The professionalised health care for chronic patients common in high income countries is very labour-intensive and expensive. Moreover, the outcomes are often poor. In low-income countries, the scarce resources and the lack of quality and continuity of health care result in high health care expenditure and very poor health outcomes. The current proposals to improve care for chronic patients in low-income countries are still very much provider-centred.The aim of this paper is to show that present provider-centred models of chronic care are not adequate and to propose 'full self-management' as an alternative for low-income countries, facilitated by expert patient networks and smart phone technology.Discussion: People with chronic life-long conditions need to 'rebalance' their life in order to combine the needs related to their chronic condition with other elements of their life. They have a crucial role in the management of their condition and the opportunity to gain knowledge and expertise in their condition and its management. Therefore, people with chronic life-long conditions should be empowered so that they become the centre of management of their condition. In full self-management, patients become the hub of management of their own care and take full responsibility for their condition, supported by peers, professionals and information and communication tools.We will elaborate on two current trends that can enhance the capacity for self-management and coping: the emergence of peer support and expert-patient networks and the development and distribution of smart phone technology both drastically expand the possibilities for full self-management.Conclusion: Present provider-centred models of care for people with chronic life-long conditions are not adequate and we propose 'full self-management' as an alternative for low-income countries, supported by expert networks and smart phone technology. © 2011 van Olmen et al; licensee BioMed Central Ltd.
Gomez H.L.,Instituto Nacional Of Enfermedades Neoplasicas |
Li R.K.,Rush University Medical Center |
Chung H.-C.,Yonsei Cancer Center |
Chan V.F.,Veterans Memorial Medical Center |
And 9 more authors.
Breast Cancer Research and Treatment | Year: 2010
Limited proven treatment options exist for patients with metastatic breast cancer (MBC) resistant to anthracycline and taxane treatment. Ixabepilone, a novel semisynthetic analog of epothilone B, has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes. In combination with capecitabine in a phase III trial (CA163-046) in this setting, ixabepilone prolonged progression-free survival and increased objective response rate relative to capecitabine (Thomas et al. J Clin Oncol 25:5210-5217, 2007). Here, we report the results of overall survival (OS), a secondary efficacy endpoint from the CA163-046 trial. Seven hundred fifty-two patients with MBC resistant to anthracyclines and taxanes were randomized to ixabepilone (40 mg/m2 intravenously on day 1 of a 21-day cycle) plus capecitabine (2,000 mg/m 2 orally on days 1 through 14 of a 21-day cycle) or capecitabine alone (2,500 mg/m2 on the same schedule). Patients receiving ixabepilone plus capecitabine treatment had a median survival of 12.9 months compared to 11.1 months for patients receiving capecitabine alone (HR = 0.9; 95%CI: 077-1.05; P = 0.19). This observed increase in median OS favored the combination; however, the difference was not statistically significant. Predefined subset analyses showed a clinically meaningful increase in OS in KPS 70-80 patients receiving ixabepilone plus capecitabine (HR = 0.75; 95% CI: 0.58-0.98). Ixabepilone plus capecitabine did not show a significant improvement in survival compared to capecitabine alone in patients with MBC resistant to anthracyclines and taxanes. The observed differences in survival favored the combination arm. A clinical benefit was also seen in patients in the KPS 70-80 subgroup (ClinicalTrials.gov number, NCT000080301). © Springer Science+Business Media, LLC. 2009.