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INTRODUCTION: The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD7442 (tixagevimab/cilgavimab) in healthy Japanese adults. METHODS: In this randomized, double-blind, placebo-controlled, phase 1 study, AZD7442 was administered intramuscularly (300 or 600 mg) or intravenously (300 or 1000 mg) to healthy Japanese adults. Primary endpoints were safety, tolerability, and pharmacokinetics. Anti-drug antibodies and neutralizing antibody activities were secondary endpoints. RESULTS: A total of 40 participants were randomized to receive AZD7442 (n = 30) or placebo (n = 10). Adverse events (AEs) occurred in 12 (40%) and 3 (30%) participants, respectively; there were no deaths, serious AEs, or AEs leading to study withdrawal. Tixagevimab and cilgavimab had mean half-lives of 82.1-95.9 and 77.9-92.0 days, respectively, which were generally similar regardless of administration route. SARS-CoV-2-neutralizing antibody titers were >4-fold higher than baseline levels from Day 8 to Day 211 in participants receiving AZD7442. CONCLUSIONS: AZD7442 was well tolerated in healthy Japanese adults, with predictable pharmacokinetics and an extended half-life, consistent with previous studies. CLINICALTRIALS: gov, NCT04896541.
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Antivirais , COVID-19 , SARS-CoV-2 , Adulto , Humanos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/farmacologia , COVID-19/terapia , Método Duplo-Cego , População do Leste Asiático , Meia-Vida , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/farmacocinética , Antivirais/farmacologia , Voluntários SaudáveisRESUMO
BACKGROUND: Long duration trial data for two-dose COVID-19 vaccines primary series' are uncommon due to unblinding and additional doses. We report one-year follow-up results from a phase 1/2 trial of AZD1222 (ChAdOx1 nCoV-19) in Japan. METHODS: Adults (n = 256) seronegative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were stratified by age, 18-55 (n = 128), 56-69 (n = 86) and ≥70-year-old (n = 42), and randomized 3:1 to AZD1222 or placebo. Safety, immunogenicity, and exploratory efficacy data were collected until study Day 365. RESULTS: Safety was consistent with previous reports. In AZD1222 vaccinees, humoral responses against SARS-CoV-2 steadily declined over time. By Day 365, anti-SARS-CoV-2 spike-binding (spike) and receptor-binding domain (RBD) mean antibody titers remained above Day 15 levels and pseudovirus neutralizing antibodies were undetectable in many participants. CONCLUSIONS: AZD1222 is immunogenic and well tolerated in Japanese adults. Expected waning in anti-SARS-CoV-2 humoral responses was observed; spike and RBD antibody titers remained elevated. (ClinicalTrials.gov: NCT04568031).
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COVID-19 , ChAdOx1 nCoV-19 , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Vacinas contra COVID-19/efeitos adversos , Japão , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Imunogenicidade da VacinaRESUMO
BACKGROUND: In Japan, regional differences in asthma mortality have been reported; however, regional differences in asthma exacerbations have not been studied extensively. Therefore, using a health insurance claims database, we investigated the regional differences in the incidence of asthma exacerbations in Japan. METHODS: This study used data from Medi-Scope (Japan Medical Information Research Institute Inc., Japan)-a nationwide health insurance claims database. Patients with asthma at the index date (the latest date of an asthma-related prescription with an asthma diagnosis before October 1, 2018) were included in the analysis. The pre-index period was defined as 1 year before the index date, and the follow-up period as 1 year after the index date. The incidence of asthma exacerbation events was analyzed for each region. RESULTS: The primary analysis population comprised 24,883 patients who were continuously prescribed ICS or ICS/LABA at least four times during the pre-index period. The incidence rate of asthma exacerbations with hospitalization was the highest in Chugoku (2.95/100 person-years [95% CI, 1.97-4.43]) and the lowest in Kanto (1.52/100 person-years [95% CI, 1.26-1.83]). The incidence rate of asthma exacerbations for the composite outcome of hospitalization, injectable corticosteroid prescription, and oral corticosteroid burst was the highest in Fukui (105.00/100 person-years [95% CI, 64.53-170.85]) and the lowest in Nagasaki (15.69/100 person-years [95% CI, 10.84-22.72]). CONCLUSIONS: Regional differences in the incidence of asthma exacerbations as well as their treatments were observed in Japan.
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Asma/epidemiologia , Hospitalização/estatística & dados numéricos , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Broncodilatadores/uso terapêutico , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Incidência , Seguro Saúde/estatística & dados numéricos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Immunogenicity and safety of the AZD1222 (ChAdOx1 nCoV-19) vaccine was evaluated in Japanese adults in an ongoing phase 1/2, randomized, double-blind, parallel-group, placebo-controlled, multi-centre trial (NCT04568031). METHODS: Adults (n=256, age ≥18 years) seronegative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were stratified by age into 18-55- (n=128), 56-69- (n=86) and ≥70-year-old cohorts (n=42), and randomized 3:1 to receive AZD1222 or placebo (two intramuscular injections 4 weeks apart). Immunogenicity and safety were coprimary endpoints. Data collected up to Day 57 are reported. RESULTS: Positive seroresponses to SARS-CoV-2 spike and receptor-binding domain antigens were seen in all 174 participants who received two doses of AZD1222. Neutralizing antibody seroresponses were seen in 67.5%, 60.3% and 50.0% of participants receiving AZD1222 aged 18-55, 56-69 and ≥70 years, respectively. Solicited adverse events (AEs) were typically mild/moderate in severity and included pain and tenderness at the injection site, malaise, fatigue, muscle pain and headache. Common unsolicited AEs included pain and tenderness at the injection site, fatigue and elevated body temperature. No vaccine-related serious AEs or deaths were reported. CONCLUSIONS: AZD1222 elicited a strong humoral immune response against SARS-CoV-2, and was well tolerated in Japanese participants, including elderly participants.
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COVID-19 , ChAdOx1 nCoV-19 , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , ChAdOx1 nCoV-19/efeitos adversos , Método Duplo-Cego , Humanos , Japão , Pessoa de Meia-Idade , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: Molecular diagnostic testing is necessary to guide optimal first-line treatment. The number of patients who receive first-line treatment based on biomarker analysis in Japan is unknown. We aimed to determine the proportion of nonsquamous non-small cell lung cancer (NSCLC) patients for whom first-line treatment was selected based on biomarker testing. METHODS: This retrospective, multicenter, observational study registered patients aged ⩾20 years with locally advanced or metastatic nonsquamous NSCLC who started first-line treatment between August and December 2017 in Japan. Data were collected from medical records between January and May 2018. The primary endpoint was the proportion of patients with confirmed biomarker status for first-line treatment decision. RESULTS: Among 202 patients enrolled from 11 centers, 161 (79.7%; 95% confidence interval, 74.2-85.2%) had confirmed biomarker status. The testing rate was highest for epidermal growth factor receptor (EGFR; 97.5%), followed by anaplastic lymphoma kinase (ALK; 88.1%), programmed death ligand-1 (PD-L1; 87.1%), and ROS1 (67.3%). For first-line treatment, 70/75 patients with EGFR-positive tumors were administered an EGFR-TKI; 14/15 patients with ALK-positive tumors received an ALK inhibitor; 2/2 patients with ROS1-positive tumors received a ROS1 inhibitor; and 29/36 driver mutation-negative patients with a PD-L1 tumor proportion score ⩾50% were administered an anti-PD-1 monoclonal antibody. Median times from confirmed diagnosis date to first-line treatment initiation, and from first biomarker test order to last biomarker test result were 19 and 11 days, respectively. CONCLUSIONS: The proportion of nonsquamous NSCLC patients with confirmed biomarker status for first-line treatment was considered insufficient and in need of improvement.
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BACKGROUND: Patients diagnosed with chronic obstructive pulmonary disease (COPD) in China are commonly prescribed ipratropium plus theophylline (I+T) therapy. Studies have shown that an inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) combination is also efficacious in reducing symptoms and exacerbations. This study evaluated the efficacy and tolerability of adding budesonide/formoterol (BUD/FORM) to I+T in Chinese patients with severe COPD. METHODS: A randomized, parallel-group, open-label, multicenter phase IV study (Clinical Trials.gov identifier: NCT01415518) was conducted in China. Patients received either BUD/FORM (160/4.5 µg; two inhalations twice daily [bid] via Turbuhaler®) + I (20 µg per inhalation, two inhalations four times daily) + T (100 mg bid) or I+T alone for 12 weeks. The primary efficacy variable was change from baseline in predose forced expiratory volume in 1 s (FEV1). RESULTS: A total of 584 patients were randomized equally between treatment groups. At the end of the study, the BUD/FORM plus I+T group displayed significant improvements in predose FEV1 versus the I+T group (between-group difference 6.9%; 95% confidence interval [CI]: 4.3, 9.6; p < 0.0001). Forced vital capacity, inspiratory capacity, peak expiratory flow and health-related quality of life (HRQoL) scores were significantly improved (all p < 0.0001) and exacerbation frequency was reduced (43.5% reduction; rate ratio 0.565, 95% CI 0.325, 0.981; p = 0.0425) with BUD/FORM plus I+T versus I+T alone. CONCLUSION: Patients with severe COPD in China treated with BUD/FORM plus I+T showed significant improvements in lung function and HRQoL and a reduction in exacerbations compared with I+T alone. Both treatments were well tolerated and no safety concerns were noted. The reviews of this paper are available via the supplemental material section.
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Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Ipratrópio/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/administração & dosagem , Idoso , Broncodilatadores/administração & dosagem , China , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
PURPOSE: A prospective, multicenter, large-scale cohort with a nested case-control study (NCT00252759) was conducted to identify and quantify risk factors for interstitial lung disease (ILD) in Japanese patients with non-small-cell lung cancer who received gefitinib. This study reports the association between gefitinib exposure and the occurrence of ILD. METHODS: A total of 1891 gefitinib plasma concentrations from 336 patients were measured after first dose, at steady state, and at time of ILD occurrence. Influences of demographic and pathophysiological factors on pharmacokinetics were investigated by non-linear mixed-effect modeling. The exposure to gefitinib was compared between patients without and with ILD occurrence to explore risks associated with gefitinib-induced ILD. Intra-patient comparison of exposure was also conducted between times at ILD development and normal states. RESULTS: In the population pharmacokinetic analysis for gefitinib, α1-acid glycoprotein (AGP), age, body weight, and concomitant use of cytochrome P450 3A4 inducers were significant covariates on oral clearance (CL/F). AGP and body weight were also identified as factors affecting the volume of distribution. CL/F was significantly lower at the time of ILD occurrence than normal states. Patients who developed ILD tended to show higher exposure to gefitinib than those without ILD; however, these differences were not statistically significant. On the other hand, exposure at the time of ILD occurrence was significantly elevated compared to the time of normal state within the same patients. CONCLUSIONS: Significant elevation of exposure of gefitinib was observed at the time of ILD occurrence, suggesting reduction of CL/F could be associated with ILD-induced AGP elevation. Increase in exposure of gefitinib is unlikely to be a robust predictor of ILD and does not warrant any dose modifications.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gefitinibe/administração & dosagem , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Gefitinibe/efeitos adversos , Gefitinibe/farmacocinética , Humanos , Japão , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Fatores de RiscoRESUMO
BACKGROUND: Quadrivalent live attenuated influenza vaccine (Q/LAIV) has not been assessed in Japanese children. OBJECTIVES: Evaluate safety and efficacy of Q/LAIV in Japanese children. PATIENTS/METHODS: Two phase 3 studies were conducted in the 2014-2015 influenza season. Study 1 was an open-label, uncontrolled single arm, multicenter study of Q/LAIV safety in subjects aged 2-6 years. Study 2 was a randomized, double-blind, placebo-controlled multicenter study of Q/LAIV safety and efficacy; subjects aged 7-18 years were randomized 2:1 to receive Q/LAIV or placebo. Primary efficacy endpoint was laboratory-confirmed symptomatic influenza infection caused by vaccine-matched strains; secondary endpoint evaluated efficacy against all strains regardless of match. Both studies reported solicited symptoms, adverse events (AEs), and serious AEs. RESULTS: In Study 1, 100 subjects received Q/LAIV. In Study 2, 1301 subjects received Q/LAIV (n = 868) or placebo (n = 433). Treatment-emergent AEs occurred in 42% of subjects in Study 1, and in 24.3% of subjects in the Q/LAIV arm and in 25.9% of subjects in the placebo arm in Study 2. In Study 2, a single infection by a vaccine-matched strain was reported in the placebo arm, resulting in a vaccine efficacy estimate of 100% (95% CI: -1875.3, 100.0); efficacy for all strains regardless of match to the vaccine was 27.5% (95% CI: 7.4, 43.0). CONCLUSIONS: Quadrivalent live attenuated influenza vaccine did not meet its primary efficacy endpoint as only a single infection by a vaccine-matched strain was detected; however, efficacy for the secondary endpoint, all strains regardless of match, was achieved. Q/LAIV was generally well tolerated in the Japanese pediatric population.
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Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Japão/epidemiologia , MasculinoRESUMO
OBJECTIVE: To estimate out-of-pocket costs and the incidence of catastrophic health expenditure in people admitted to hospital with acute coronary syndromes in Asia. METHODS: Participants were enrolled between June 2011 and May 2012 into this observational study in China, India, Malaysia, Republic of Korea, Singapore, Thailand and Viet Nam. Sites were required to enrol a minimum of 10 consecutive participants who had been hospitalized for an acute coronary syndrome. Catastrophic health expenditure was defined as out-of-pocket costs of initial hospitalization > 30% of annual baseline household income, and it was assessed six weeks after discharge. We assessed associations between health expenditure and age, sex, diagnosis of the index coronary event and health insurance status of the participant, using logistic regression models. FINDINGS: Of 12,922 participants, 9370 (73%) had complete data on expenditure. The mean out-of-pocket cost was 3237 United States dollars. Catastrophic health expenditure was reported by 66% (1984/3007) of those without insurance versus 52% (3296/6366) of those with health insurance (P < 0.05). The occurrence of catastrophic expenditure ranged from 80% (1055/1327) in uninsured and 56% (3212/5692) of insured participants in China, to 0% (0/41) in Malaysia. CONCLUSION: Large variation exists across Asia in catastrophic health expenditure resulting from hospitalization for acute coronary syndromes. While insurance offers some protection, substantial numbers of people with health insurance still incur financial catastrophe.
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Síndrome Coronariana Aguda/economia , Doença Catastrófica/economia , Efeitos Psicossociais da Doença , Financiamento Pessoal , Gastos em Saúde , Idoso , Ásia , Sudeste Asiático , China , Feminino , Gastos em Saúde/estatística & dados numéricos , Humanos , Índia , Masculino , Pessoas sem Cobertura de Seguro de Saúde , Pessoa de Meia-Idade , Estudos Prospectivos , República da CoreiaRESUMO
BACKGROUND: In the Study to Investigate Real Life Effectiveness of Symbicort Maintenance and Reliever Therapy in Asthma Patients Across Asia, the effectiveness of single-inhaler budesonide/formoterol maintenance and reliever therapy was evaluated in patients with poorly controlled asthma. OBJECTIVE: To study the effects of this therapy on a Chinese patient subgroup. METHODS: In this 12-week, multicenter, open-label therapeutic phase IV study, patients with partially controlled or uncontrolled asthma were switched from their usual asthma treatment to budesonide/formoterol (160/4.5 µg, one inhalation twice daily and as needed) after a 2-week run-in period. Primary and secondary objectives of the study, asthma control and quality of life were assessed by using the five-item Asthma Control Questionnaire and the Standardized Asthma Quality of Life Questionnaire. Asthma symptom scores, study medication use, asthma control and/or symptom-free days, and the number of asthma-related nighttime awakenings were also monitored. RESULTS: In total, 478 Chinese patients were enrolled and 407 patients initiated treatment. The patients displayed a significant improvement in mean (standard deviation) five-item Asthma Control Questionnaire (-0.58 ± 0.86; p < 0.0001) and Standardized Asthma Quality of Life Questionnaire (0.69 ± 0.79; p < 0.0001) scores versus the run-in period. Mean (standard deviation) asthma symptom scores were significantly reduced compared with run-in (-0.30 ± 0.55 daytime, -0.31 ± 0.56 nighttime; p < 0.0001 for both), as was as-needed study medication use (-0.24 ± 1.16 daytime, -0.28 ± 0.97 nighttime; p < 0.0001 for both). Patients who received previous treatment with salmeterol/fluticasone propionate also showed improvement in asthma control. CONCLUSIONS: In China, asthma control in Chinese patients whose asthma was not fully controlled with previous standard therapy improved during 12 weeks of treatment with budesonide/formoterol maintenance and reliever therapy. Quality of life was improved, and treatment was well tolerated. (Clinical Trials identifier NCT00939341).
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Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Budesonida/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Adolescente , Adulto , Idoso , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Asma/diagnóstico , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Quimioterapia Combinada , Feminino , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Testes de Função Respiratória , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Triple combination therapy with tiotropium plus budesonide/formoterol has improved lung function and reduced exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) in Western countries, but no such data exist for East Asian patients. This study aimed to evaluate the efficacy and tolerability of adding budesonide/formoterol to tiotropium compared with tiotropium alone in East Asian patients with severe/very severe COPD. METHODS: This 12-week, randomized, parallel-group, multicentre, open-label study was conducted in East Asia. After a 14-day run-in period during which patients received tiotropium 18 µg once daily, patients were randomized to tiotropium (18 µg once daily) + budesonide/formoterol (160/4.5 µg 2 inhalations twice daily) or tiotropium alone (18 µg once daily). The primary endpoint was change from baseline in pre-dose forced expiratory volume in 1 s (FEV1 ) to the mean of values measured at Weeks 1, 6 and 12. RESULTS: Pre-dose FEV1 significantly increased from baseline with tiotropium plus budesonide/formoterol (n = 287) versus tiotropium alone (n = 291) (5.0% vs 0.6%; treatment difference: 4.4% (95% CI: 1.9-6.9), P = 0.0004). Triple therapy also reduced the COPD exacerbation rate by 40.7% (P = 0.0032) and prolonged time to first exacerbation (38.6% risk reduction, P = 0.0167) versus tiotropium alone and markedly improved health-related quality of life (HRQoL), measured using the St George's Respiratory Questionnaire. Incidence of adverse events was 26% for both groups. CONCLUSIONS: In East Asian patients with severe/very severe COPD, adding budesonide/formoterol to tiotropium was associated with significant improvements in FEV1 and HRQoL and lower COPD exacerbation rates. Treatment was generally well tolerated. CLINICAL TRIAL REGISTRATION: NCT01397890 at Clinicaltrials.gov.
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Combinação Budesonida e Fumarato de Formoterol , Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Brometo de Tiotrópio , Idoso , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Combinação Budesonida e Fumarato de Formoterol/efeitos adversos , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada/métodos , Ásia Oriental , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/psicologia , Índice de Gravidade de Doença , Exacerbação dos Sintomas , Brometo de Tiotrópio/administração & dosagem , Brometo de Tiotrópio/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Monthly goserelin 3.6 mg dosing suppresses estradiol (E2) production and has proven efficacy in pre-menopausal women with estrogen receptor (ER)-positive breast cancer. This non-inferiority study evaluated the efficacy and safety of 3-monthly goserelin 10.8 mg compared with monthly goserelin 3.6 mg. METHODS: This was a Phase 3, open-label, multicenter trial. Pre-menopausal women with ER-positive advanced breast cancer were randomized to 3-monthly goserelin 10.8 mg or monthly goserelin 3.6 mg; all patients received concomitant tamoxifen (20 mg daily). The primary endpoint was progression-free survival (PFS) rate at 24 weeks; non-inferiority was to be confirmed if the entire 95 % confidence interval (CI) for the treatment difference was above -17.5 %. Secondary endpoints included objective response rate (ORR), serum E2 levels, safety, and tolerability. RESULTS: In total, 222 patients were randomized (goserelin 10.8 mg, n = 109; goserelin 3.6 mg, n = 113). PFS rate at week 24 was 61.5 % (goserelin 10.8 mg) and 60.2 % (goserelin 3.6 mg); treatment difference (95 % CI) was 1.3 % (-11.4, 13.9), confirming non-inferiority of goserelin 10.8 mg compared with goserelin 3.6 mg. ORR was 23.9 % (goserelin 10.8 mg) and 26.9 % (goserelin 3.6 mg); treatment difference (95 % CI) was -3.0 % (-15.5, 9.7). At week 24, mean serum E2 concentrations were similar in the goserelin 10.8 mg and goserelin 3.6 mg groups (20.3 pg/mL and 24.8 pg/mL, respectively). CONCLUSION: A regimen of 3-monthly goserelin 10.8 mg demonstrated non-inferiority compared with monthly goserelin 3.6 mg for PFS rate at 24 weeks, with similar pharmacodynamic and safety profiles, in pre-menopausal women with ER-positive breast cancer.
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Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Gosserrelina/administração & dosagem , Gosserrelina/uso terapêutico , Adulto , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Gosserrelina/efeitos adversos , Gosserrelina/farmacocinética , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Receptores de Estrogênio/metabolismo , Tamoxifeno/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: In-hospital and postdischarge mortality for acute coronary syndromes (ACS) vary across Asia and remain generally poorer than globally. The relationship between real-life antithrombotic management patterns (AMPs) and ACS-related outcomes in Asia is unclear. METHODS: EPICOR Asia (Long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) (NCT01361386) is a prospective, multinational, observational study of patients discharged after hospitalization for an ACS, with 2-year follow-up. The aim is to describe short- and long-term (up to 2 years post-index event) AMPs in patients hospitalized for ACS and to record clinical outcomes, healthcare resource use, and self-reported health status. Pre- and in-hospital management, AMPs, and associated outcomes, with particular focus on ischemic and bleeding events, will be recorded during the 2-year follow up. RESULTS: Between June 2011 and May 2012, 13 005 patients were enrolled. From these, 12 922 patients surviving an ACS (6616 with STEMI, 2570 with NSTEMI, and 3736 with UA) were eligible for inclusion from 219 hospitals across 8 countries and regions in Asia: China (n = 8214), Hong Kong (n = 177), India (n = 2468), Malaysia (n = 100), Singapore (n = 93), South Korea (n = 705), Thailand (n = 957), and Vietnam (n = 208). CONCLUSIONS: EPICOR Asia will provide information regarding clinical management and AMPs for ACS patients in Asia. Impact of AMPs on clinical outcomes, healthcare resource use, and self-reported health status both during hospitalization and up to 2 years after discharge will also be described.
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Síndrome Coronariana Aguda/tratamento farmacológico , Angina Instável/tratamento farmacológico , Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Padrões de Prática Médica/tendências , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Angina Instável/diagnóstico , Angina Instável/mortalidade , Anticoagulantes/efeitos adversos , Ásia/epidemiologia , Protocolos Clínicos , Quimioterapia Combinada , Feminino , Fibrinolíticos/efeitos adversos , Seguimentos , Recursos em Saúde/estatística & dados numéricos , Nível de Saúde , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Alta do Paciente , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , Autorrelato , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients necessitates accurate, timely testing. Although EGFR mutation testing has been adopted by many laboratories in Asia, data are lacking on the proportion of NSCLC patients tested in each country, and the most commonly used testing methods. METHODS: A retrospective survey of records from NSCLC patients tested for EGFR mutations during 2011 was conducted in 11 Asian Pacific countries at 40 sites that routinely performed EGFR mutation testing during that period. Patient records were used to complete an online questionnaire at each site. RESULTS: Of the 22,193 NSCLC patient records surveyed, 31.8% (95% confidence interval: 31.2%-32.5%) were tested for EGFR mutations. The rate of EGFR mutation positivity was 39.6% among the 10,687 cases tested. The majority of samples were biopsy and/or cytology samples (71.4%). DNA sequencing was the most commonly used testing method accounting for 40% and 32.5% of tissue and cytology samples, respectively. A pathology report was available only to 60.0% of the sites, and 47.5% were not members of a Quality Assurance Scheme. CONCLUSIONS: In 2011, EGFR mutation testing practices varied widely across Asia. These data provide a reference platform from which to improve the molecular diagnosis of NSCLC, and EGFR mutation testing in particular, in Asia.
Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Análise Mutacional de DNA/métodos , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Ásia/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , DNA de Neoplasias/genética , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Estadiamento de Neoplasias , Ilhas do Pacífico/epidemiologia , Reação em Cadeia da Polimerase , Prognóstico , Kit de Reagentes para Diagnóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: PIONEER (NCT01185314) was a prospective, multinational, epidemiological study of epidermal growth factor receptor (EGFR) mutations in patients from Asia with newly diagnosed advanced lung adenocarcinoma. METHODS: Eligible patients (aged ≥20 years) had untreated stage IIIB/IV adenocarcinoma. The EGFR mutation status (primary end point: positive, negative, or undetermined) of tumor samples (biopsy, surgical specimen, or cytology) was determined (Scorpion amplification refractory mutation system). EGFR mutation frequency was calculated and compared between demographic and clinical subgroups. RESULTS: Of 1482 patients from seven Asian regions, 43.4% of patients were female, median age was 60 years (range, 17-94), and 52.6% of patients were never-smokers. EGFR mutation status was evaluable in tumors from 1450 patients (97.8%) (746 [51.4%] positive; 704 [48.6%] negative). Country, sex, ethnicity, smoking status, pack-years (all p < 0.001), disease stage (p = 0.009), and histology type (p = 0.016) correlated significantly with EGFR mutation frequency. Mutation frequency was 61.1% in females, 44.0% in males; lower in patients from India (22.2%) compared with other areas (47.2%-64.2%); highest among never-smokers (60.7%); and decreased as pack-year number increased (>0-10 pack-years, 57.9%; >50 pack-years, 31.4%) (similar trend by sex). Ethnic group (p < 0.001) and pack-years (p < 0.001) had statistically significant associations with mutation frequency (multivariate analysis); sex was not significant when adjusted for smoking status. CONCLUSION: PIONEER is the first prospective study to confirm high EGFR mutation frequency (51.4% overall) in tumors from Asian patients with adenocarcinoma. The observed high mutation frequency in demographic/clinical subgroups compared with white populations suggests that mutation testing should be considered for all patients with stage IIIB/IV adenocarcinoma, even males and regular smokers, among Asian populations.
Assuntos
Adenocarcinoma Bronquioloalveolar/genética , Adenocarcinoma/genética , Povo Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação/genética , Adenocarcinoma/secundário , Adenocarcinoma Bronquioloalveolar/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Carotid intima media thickness (CIMT) is a surrogate marker for atherosclerosis, used to identify asymptomatic individuals at increased risk of cardiovascular events. The primary objective of this study was to obtain the distribution of CIMT measurements in Asian individuals with cardiovascular disease (CVD) risk factors who were not receiving lipid-lowering agents. METHODS: Mean CIMT based on ultrasonographic measurement of 12 sites within the common carotid artery was recorded for 2726 subjects across eight Asian countries who had two or more CVD risk factors but were not receiving lipid-lowering therapy. CVD risk factors and lipid and glucose profiles were analyzed with respect to distribution of CIMT and high-sensitivity C-reactive protein (hs-CRP) values. RESULTS: The overall mean (SD) of mean CIMT (mean-mean CIMT) was 0.662 (0.16) mm. There was a significant variation in mean-mean CIMT across countries (P<0.0001). Mean-mean CIMT values (mm) by age were: 0.485, 0.527, 0.614, 0.665, 0.715 and 0.797 for ≤ 29, 30-39, 40-49, 50-59, 60-69 and ≥ 70 years, respectively. Multivariate analyses confirmed a significant association between increasing mean-mean CIMT and increasing age, male gender, low high-density lipoprotein-cholesterol (HDL-C) levels and elevated fasting blood glucose levels. Analysis of log-transformed hs-CRP levels showed significant association with increasing waist circumference, low-density lipoprotein-cholesterol, body-mass index, high blood glucose levels and low HDL-C. CONCLUSIONS: Our data show normative mean-mean CIMT data for Asian subjects with two or more CVD risk factors who are not receiving lipid-lowering therapy, which may guide CVD risk-stratification of asymptomatic individuals in Asia.
Assuntos
Aterosclerose/epidemiologia , Aterosclerose/patologia , Espessura Intima-Media Carotídea , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: In IPASS (IRESSA Pan-Asia Study), clinically selected patients with pulmonary adenocarcinoma received first-line gefitinib or carboplatin/paclitaxel. This preplanned, exploratory analysis was conducted to increase understanding of the use of surrogate samples, such as serum, versus tumor biopsy samples for determining EGFR mutation status in the Japanese cohort (n = 233). METHODS: EGFR mutations were assessed using tumor tissue-derived DNA (n = 91) and circulating free (cf) DNA from pretreatment serum samples (n = 194). RESULTS: Fewer patients were EGFR mutation positive when assessed using pretreatment cfDNA (23.7%) versus tumor tissue-derived DNA (61.5%). cfDNA results identified no false positives but a high rate of false negatives (56.9%). There was a significant interaction between cfDNA EGFR mutation status and treatment for progression-free survival (PFS) (p = 0.045). PFS was significantly longer and objective response rate (ORR) higher with gefitinib than carboplatin/paclitaxel in the cfDNA EGFR mutation-positive subgroup (PFS: hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.14-0.60; p < 0.001; ORR: odds ratio [OR], 1.71; 95% CI, 0.48-6.09; 75.0% versus 63.6%; p = 0.40). There was a slight numerical advantage in PFS and ORR for gefitinib over carboplatin/paclitaxel in the cfDNA EGFR mutation-negative subgroup, likely due to the high rate of false negatives within this subgroup. CONCLUSIONS: These results merit further investigation to determine whether alternative sources of tumor DNA, such as cfDNA in serum, could be used for determining EGFR mutation status in future; currently, where a sample is available, analysis of tumor material is recommended.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Resinas Acrílicas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/sangue , Análise Mutacional de DNA , Intervalo Livre de Doença , Receptores ErbB/sangue , Reações Falso-Negativas , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Paclitaxel/administração & dosagem , Polivinil/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: This post hoc analysis investigated the relationship between tumor response and overall survival (OS) in pretreated advanced non-small cell lung cancer (NSCLC). METHODS: We conducted landmark survival analyses of V-15-32, a phase III study comparing gefitinib with docetaxel in pretreated advanced NSCLC. Best response at weeks 8, 12, 16, and 20, and visit response at week 4, were evaluated. RESULTS: Disease control (DC; complete response [CR], partial response [PR], or stable disease) was a better predictor of OS than CR/PR at all time points. The strongest predictor of OS for both gefitinib and docetaxel was DC at week 8 (hazard ratio [HR] DC versus non-DC: 0.30, 95% confidence interval [CI] 0.20-0.45, p < 0.001 for both treatments). DC at week 4 was also associated with longer survival compared with non-DC for both treatments (HR 0.33, 95% CI 0.23-0.49, p < 0.001 for gefitinib; HR 0.30, 95% CI 0.19-0.47, p < 0.001 for docetaxel). DISCUSSION: DC is a better predictor of OS with gefitinib and docetaxel than CR/PR in advanced pretreated NSCLC, with a best response of DC at week 8 the strongest predictor.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel , Gefitinibe , Humanos , Neoplasias Pulmonares/patologia , Quinazolinas/administração & dosagem , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
PURPOSE: This phase III study (V-15-32) compared gefitinib (250 mg/d) with docetaxel (60 mg/m(2)) in patients (N = 489) with advanced/metastatic non-small-cell lung cancer (NSCLC) who had failed one or two chemotherapy regimens. METHODS: The primary objective was to compare overall survival to demonstrate noninferiority for gefitinib relative to docetaxel. An unadjusted Cox regression model was used for the primary analysis. RESULTS: Noninferiority in overall survival was not achieved (hazard ratio [HR], 1.12; 95.24% CI, 0.89 to 1.40) according to the predefined criterion (upper CI limit for HR Assuntos
Antineoplásicos/uso terapêutico
, Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
, Neoplasias Pulmonares/tratamento farmacológico
, Quinazolinas/uso terapêutico
, Taxoides/uso terapêutico
, Idoso
, Carcinoma Pulmonar de Células não Pequenas/mortalidade
, Docetaxel
, Feminino
, Gefitinibe
, Humanos
, Neoplasias Pulmonares/mortalidade
, Masculino
, Pessoa de Meia-Idade
, Modelos de Riscos Proporcionais
, Análise de Sobrevida