RESUMEN
ABSTRACT: This meta-analysis evaluates the efficacy and safety of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). We searched MEDLINE, Embase, and Cochrane databases until July 2023 for trials assessing CAR T-cell therapies and CD20×CD3 bispecific antibodies as third or subsequent lines in R/R DLBCL. Random-effects models estimated the complete response (CR) rate and secondary outcomes, with meta-regressions adjusting for relevant covariates. Sixteen studies comprising 1347 patients were included in the pooled analysis. The pooled CR rate for bispecific antibodies was 0.36 (95% confidence interval [CI], 0.29-0.43), compared with 0.51 (95% CI, 0.46-0.56) for CAR T-cell therapy (P < .01). This superiority persisted when comparing the CAR T-cell-naive patients within the bispecific antibody group, with a CR rate of 0.37 (95% CI, 0.32-0.43). Multivariable meta-regression also revealed better efficacy of CAR T cells with adjustment for the proportion of double-hit lymphoma. The pooled 1-year progression-free survival rate mirrored these findings (0.32 [95% CI, 0.26-0.38] vs 0.44 [95% CI, 0.41-0.48]; P < .01). For adverse events of grade ≥3, the bispecific antibody had incidences of 0.02 (95% CI, 0.01-0.04) for cytokine release syndrome, 0.01 (95% CI, 0.00-0.01) for neurotoxicity, and 0.10 (95% CI, 0.03-0.16) for infections. The CAR T cell had rates of 0.08 (95% CI, 0.03-0.12), 0.11 (95% CI, 0.06-0.17), and 0.17 (95% CI, 0.11-0.22), respectively, with significant differences observed in the first 2 categories. In summary, CAR T-cell therapy outperformed bispecific antibody in achieving higher CR rates, although with an increase in severe adverse events.
Asunto(s)
Anticuerpos Biespecíficos , Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/efectos adversos , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/inmunología , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunologíaRESUMEN
Telehealth has been widely adopted during the COVID-19 pandemic, and this article examines challenges faced by telephone interpreters in working with healthcare providers in the context of the Australian healthcare system. Based on one-on-one interviews with 67 healthcare interpreters in Australia, it explores various elements which affect communication processes in telephone interpreting and interpreters' views on healthcare providers' abilities to collaborate with interpreters. Data analysis indicates that telephone interpreting is often affected by a lack of briefing, poor acoustics and the absence of visual cues. While these factors pose significant challenges to telephone interpreters, a provider's tendency to see interpreters as 'translation machines' was perceived as a deeper underlying problem by the interpreters. The mechanistic approaches to interpreting among healthcare providers pose barriers to interpreter-provider collaboration and exacerbate communication problems caused by the external elements in telephone-interpreted encounters. The article calls for urgent need to raise awareness of interpreting among healthcare providers as a key to ensuring desirable health outcomes for patients from minority backgrounds.
Asunto(s)
COVID-19 , Traducción , Humanos , Barreras de Comunicación , Pandemias , Relaciones Médico-Paciente , Australia , TeléfonoRESUMEN
PURPOSE: We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis. Materials and Methods: R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment. RESULTS: Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment. CONCLUSION: Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/uso terapéutico , Inmunoterapia Adoptiva/efectos adversos , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Recuperativa , Recurrencia Local de Neoplasia/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológicoRESUMEN
INTRODUCTION: Thymic epithelial tumors (TETs) are rare but are the most common tumors of the anterior mediastinum. Platinum-based combination chemotherapy is the standard of care for such tumors and is associated with a 50% to 90% objective response rate (ORR) in metastatic disease. Nevertheless, there is no standard chemotherapeutic option after failure of platinum-based combination chemotherapy. Genetic alterations associated with the cell cycle, including pRB, p16INK4A, and cyclin D1, are most often observed in TETs. On the basis of these results, we conducted a phase 2 trial to evaluate the efficacy and safety of palbociclib in patients with recurrent or refractory advanced TETs. METHODS: This is a phase 2, multicenter, open-label, single-arm study of palbociclib monotherapy in patients with recurrent or metastatic advanced TETs who failed one or more cytotoxic chemotherapies. The patients received 125 mg of oral palbociclib daily for 21 days, followed by a 7-day break. The primary end point was progression-free survival (PFS). The secondary end points were ORR, duration of response, overall survival, and safety. RESULTS: Between August 2017 and October 2019, a total of 48 patients were enrolled. The median number of previous chemotherapies was one (range: one to four), and 21 (43.7%) of 48 patients received thymectomy. By the WHO classification, the patients were type A (n = 1), type B1 (n = 2), type B2 (n = 8), type B3 (n = 13), thymic carcinoma (n = 23), and unknown (n = 1). With a median follow-up of 14.5 months (range: 0.8-38.2), the median number of cycles of palbociclib monotherapy was 10 (range: 1-40). The ORR was 12.5% (four partial responses in thymoma and two partial responses in thymic carcinoma). The PFS at 6 months was 60.2%, and the median PFS was 11.0 months (95% confidence interval: 4.6-17.4). The median overall survival was 26.4 months (95% confidence interval: 17.4-35.4). The most common treatment-related adverse events of any grade were neutropenia (62.5%), anemia (37.5%), and thrombocytopenia (29.1%), and the most common grade 3/4 treatment-related hematologic adverse event was neutropenia (41.7%). Neutropenia above grade 3 was reversible, and there were no cases with neutropenic fever. CONCLUSIONS: Palbociclib monotherapy was well tolerated and had encouraging efficacy in patients with TETs who failed platinum-based combination chemotherapy.
Asunto(s)
Neoplasias Pulmonares , Neoplasias Glandulares y Epiteliales , Neutropenia , Timoma , Neoplasias del Timo , Humanos , Timoma/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias del Timo/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Background: Although smoking status has potential as a biomarker for immune checkpoint blockade in advanced non-small cell lung cancer (NSCLC), its clinical significance remains obscure. This meta-analysis aims to assess the impact of the smoking status on the efficacy of first-line immunotherapy and to find better treatment in never-smoker and ever-smoker patients. Methods: We searched the MEDLINE, EMBASE, and Cochrane database for trials comparing immunotherapy with conventional chemotherapy as front-line treatment for advanced NSCLC. Random-effects models were used to pool estimates of hazard ratios (HRs) for overall survival with 95% confidence intervals (CIs). Predefined subgroup analysis was performed to investigate the difference in the efficacy between the single checkpoint blockade and checkpoint inhibitor plus chemotherapy combination in the never-smokers and current/former smokers. Results: Twelve trials involving 6,446 patients were included in the analysis. A statistically significant overall survival benefit over conventional chemotherapy was found for both checkpoint inhibitor monotherapy (HR, 0.71; 95% CI, 0.59-0.85) and checkpoint inhibitor plus chemotherapy (HR, 0.75; 95% CI, 0.63-0.90) in the current/former smoker group. There was no subgroup difference between monotherapy and combination treatment (p=0.67). However, there was an inconsistent survival outcome in the never-smoker group; checkpoint blockade monotherapy did not show significantly better efficacy than chemotherapy alone (HR, 1.05; 95% CI, 0.81-1.37), but combination treatment showed an overall survival benefit (HR, 0.64; 95% CI, 0.43-0.94). A significant subgroup difference existed between monotherapy and combination therapy (p=0.04). Similarly, there was a significant difference in efficacy of monotherapy between the current/former smoker and never-smoker group (p=0.01), but the efficacy of the combination treatment was comparable between the two groups (p=0.45). Conclusion: Smoking status, which is easily available information, could be used as a guide in clinical practice to choose better treatment in the front-line setting for advanced NSCLC patients.
RESUMEN
Peripheral T-cell lymphomas (PTCLs) are known to have an aggressive clinical course and grave prognosis. Several recommended first-line treatment regimens are available, but identification of the superior treatment remain elusive. We conducted a systematic review and meta-analysis to determine which study-level factors and group of regimens affect survival outcomes. The MEDLINE, Embase, and Cochrane databases were searched from inception to January 2021, and phase II or III clinical studies evaluating the efficacy of chemotherapy regimens were included. Random effects models were used to estimate 3-year overall survival rate, complete remission rate, and subgroup differences. Meta-regressions were carried out with adjustments for relevant covariates. Overall, 34 cohorts from 28 studies comprising 1424 PTCL patients were included in the pooled analysis. Chemotherapy regimens were divided into four groups: cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), CHOP plus etoposide, gemcitabine-based, and others. The pooled 3-year overall survival rate was 0.49 (95% confidence interval [CI] 0.43-0.54) for CHOP, 0.61 (95% CI 0.52-0.70) for CHOP plus etoposide, 0.39 (95% CI 0.30-0.47) for gemcitabine-based, and 0.61 (95% CI 0.44-0.78) for others. CHOP plus etoposide was significantly better than CHOP, with the latter used as a reference (coefficient of 0.11; p = 0.035), with adjustment for the proportion of International Prognostic Index score 4-5 in meta-regression analysis. Although grossly divided groups were pooled and analyzed, among four regimen groups for frontline PTCL treatment CHOP plus etoposide showed better survival than CHOP.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células T Periférico/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/clasificación , Humanos , Linfoma de Células T Periférico/patología , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Pericardiocentesis (PCC) with extended catheter drainage has become a relatively safe procedure to control pericardial effusion (PE), but little is known about long-term outcomes after PCC in malignant PE. OBJECTIVES: This study evaluated the effects of anti-inflammatory agents on long-term outcomes after effective drainage of PE in active cancer patients. METHODS: From May 2007 to December 2018, 445 patients with malignant PE who underwent echocardiography-guided PCC were enrolled. Clinical, laboratory, echocardiographic and procedural findings, and clinical outcome data were collected. Use of anti-inflammatory agents including colchicine, nonsteroidal anti-inflammatory drugs, or steroids after PCC was also analyzed. Colchicine was administered in a dose of 0.6 mg orally, twice a day for 2 months. The primary outcome was defined as a composite of all-cause death and re-PCC or pericardial window operation due to recurred PE. RESULTS: The procedure was successful in 97.0% of the cases, with 1 procedure-related death. During the follow-up of 2 years, 26.1% of patients developed recurrent PE, and 46.0% developed constrictive pericarditis. The colchicine treatment group showed a significantly lower risk of composite events (adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [CI]: 0.49 to 0.87; p = 0.003) as well as all-cause death (aHR: 0.60; 95% CI: 0.45 to 0.81; p = 0.001) than did the noncolchicine group. On propensity score matching, colchicine after PCC was consistently associated with a lower composite events (aHR: 0.55; 95% CI: 0.37 to 0.82; p = 0.003). CONCLUSIONS: In cancer patients with malignant PE, PCC with extended drainage can be an appropriate therapeutic option and shows low complication rate. Patients receiving colchicine after successful PCC showed significant improvement in clinical outcome.
Asunto(s)
Colchicina/uso terapéutico , Neoplasias/complicaciones , Derrame Pericárdico/cirugía , Pericardiocentesis/efectos adversos , Pericarditis Constrictiva/prevención & control , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Derrame Pericárdico/etiología , Pericarditis Constrictiva/epidemiología , Pericarditis Constrictiva/etiología , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
PURPOSE: We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors, including a baseline mini nutritional assessment short form (MNA-SF) score, of response and survival. PATIENTS AND METHODS: Between 2010 and 2018, 96 AML patients aged 65 and above who received decitabine treatment at 6 centers in Korea were retrospectively evaluated. Response rates, hematologic improvements (HI), progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The median age at diagnosis was 73.9 years, and the median number of decitabine treatments administered to the patients was 4 (range, 1-29). Of 85 patients, 15 patients (17.6%) achieved complete remission (CR) or CR with incomplete blood count recovery. Twelve patients (14.1%) showed partial remission (PR), and 18 (21.2%) demonstrated HI without an objective response. The median PFS and OS were 7.0 (95% confidence interval [CI], 4.9-9.0) and 10.6 (95% CI, 7.7-13.5%) months, respectively. In multivariate analyses, MNA-SF score ≥ 8 and the absence of peripheral blood (PB) blasts were significant predictors for improved PFS and OS. CONCLUSIONS: For older patients with newly diagnosed AML, a high MNA-SF score and the absence of PB blasts were independently associated with improved survival.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Decitabina/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Inducción de Remisión/métodos , Factores de Edad , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Recuento de Células Sanguíneas , Médula Ósea/patología , Decitabina/efectos adversos , Esquema de Medicación , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Evaluación Nutricional , Supervivencia sin Progresión , República de Corea/epidemiología , Estudios Retrospectivos , Pérdida de PesoRESUMEN
Head and neck cancer (HNC) is characterized with multiple aberrations in cell cycle pathways, including amplification of cyclin D1. Palbociclib (PAL), a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has been reported to regulate cell cycle progression in HNC. However, recent studies have revealed the acquired resistance of certain cells to PAL through activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Therefore, we investigated whether the inhibition of MEK/ERK pathway by trametinib (TRA) may overcome the limited efficacy of PAL in HNC. We evaluated the effect of PAL alone and in combination with TRA on the viability of HNC cells, and found that the combination treatment synergistically inhibited the proliferation of HNC cells. The combination treatment induced G0/G1 cell cycle arrest and apoptotic cell death. In particular, apoptosis mediated by the combination treatment was accompanied with an increase in caspase-3 activity and the number of TUNEL-positive apoptotic cells. These results were consistent with the decrease in cell cycle progression and mitogen-activated protein kinase (MAPK) pathway activation. In a xenograft mouse model of HNC, PAL and TRA synergistically inhibited tumor growth and enhanced tumor cell apoptosis, consistent with the increase in the number of TUNEL-positive cells. The anti-proliferative effects were evident in tumor tissues subjected to the combination treatment as compared with those treated with single drug. Taken together, our study demonstrates that the combination of PAL and TRA exerts synergistic anticancer effects and inhibits cell cycle check points and MEK/ERK pathway in HNC, suggestive of their potential application for HNC treatment.
RESUMEN
PURPOSE: The objective of this literature review was to analyze the cumulative survival rates (CSRs) of rigid and non-rigid double-crown-retained removable dental prostheses. MATERIALS AND METHODS: Screening of the literature published from January 1995 to December 2019 was performed by using electronic data base (Pubmed) and manual search. The CSRs of rigid and non-rigid double crown removable dental prostheses were investigated. RESULTS: A total of 403 articles were reviewed and 56 relevant articles of them were selected. Subsequently, 25 articles were included for data extraction. These articles were classified according to rigid and non-rigid type double crowns and further subdivided into teeth, implants, and teeth-implant combination types. The CSRs of rigid type double crown ranged from 68.9% to 95.1% of 5 to 10 years in tooth abutments, 94.02% to 100% over a 3-year mean observation periods in implant abutments, and 81.8% to 97.6% in tooth-implant combination. Non-rigid type double crowns had various CSR ranges from 34% to 94% maximum during 10 years observation in teeth abutment. The CSRs of non-rigid type had over 98% in implant abutments, and ranged from 85% to 100% in tooth-implant combination. CONCLUSION: The CSRs of double crowns varies according to types. With accurate evaluation of the remaining teeth and plan of the strategic implant placement, it could be successful treatment alternatives for partially or completely edentulous patients.
RESUMEN
Although anti-programmed death-1 (PD-1) treatment has shown remarkable anti-tumor efficacy, immune-related adverse events (irAEs) develop with heterogeneous clinical manifestations. However, the immunological understanding of irAEs is currently limited. In the present study, we analyzed peripheral blood T cells obtained from cancer patients who received anti-PD-1 treatment to determine the immunological characteristics of irAEs. This study included 31 patients with refractory thymic epithelial tumor (TET) who were enrolled in a phase II trial of pembrolizumab (NCT02607631) and 60 patients with metastatic non-small cell lung cancer (NSCLC) who received pembrolizumab or nivolumab. T-cell profiling was performed by multicolor flow cytometry using peripheral blood obtained before treatment and 7 days after the first dose of anti-PD-1 antibodies. irAEs developed in 21 TET patients and 24 NSCLC patients. Severe (≥ grade 3) irAEs occurred in 7 TET patients (22.6%) and 6 NSCLC patients (10.0%). Patients with severe irAEs exhibited a significantly lower fold increase in the frequency of effector regulatory T (eTreg) cells after anti-PD-1 treatment, a higher ratio of T helper-17 (Th17) and T helper-1 cells at baseline, and a higher percentage of Ki-67+ cells among PD-1+CD8+ T cells posttreatment. In clustering analysis using the T-cell parameters, patients with irAEs were grouped into four distinct subtypes: Th17-related, TNF-related, CD8-related Treg-compensated, and CD8-related Treg-uncompensated. The T-cell parameters showed a predictive value for the development of each subtype of severe irAEs. In conclusion, severe irAEs after anti-PD-1 treatment were clustered into four immunological subtypes, and potential biomarkers for early prediction of severe irAEs were proposed.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Linfocitos T CD8-positivos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/efectos adversos , Receptor de Muerte Celular Programada 1RESUMEN
Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment. Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39+ cells among CD8+ T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39+CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.
RESUMEN
PURPOSE: To evaluate the effect of periodontal and prosthodontic therapy on glycated hemoglobin A(HbA1c) level in patients with diabetes. MATERIALS AND METHODS: This is a retrospective study of 70 patients suffering from diabetes who visited the Kyungpook National University Hospital between January 2016 and May 2018. Patients underwent medical evaluation for their routine check-up, which includes laboratory test for HbA1c levels. Among the 70 patients, 35 patients also visited Kyungpook National University Dental Hospital during the same period to receive periodontal and prosthodontic therapy, while the other 35 patients did not receive such therapy. The HbA1c levels were compared before and after periodontal and prosthodontic therapy. Comparisons between groups and within groups were performed using independent t-test. RESULTS: The HbA1c levels in the group who have received periodontal and prosthodontic therapy decreased from 7.2 to 6.7 (P=.001). The HbA1c levels in the control group decreased from 7.2 to 7.1 (P=.580). The difference in changes between the two patient groups was statistically significant (P=.011). CONCLUSION: Periodontal and prosthodontic therapy can be effective on glycemic control in patients with diabetes.
RESUMEN
As it is recommended that most assessments for treatment-free remission (TFR) in patients with chronic myeloid leukemia be conducted as prospective trials, we conducted a systematic review and meta-analysis to investigate which study-level factors affected the TFR rate. The MEDLINE, Embase, and Cochrane databases were systematically searched from inception to July 2018. A random effect model was used to estimate the overall mean TFR rate, subgroup differences, and regression coefficients with continuous variables. Overall, 12 tyrosine kinase inhibitor (TKI) stopping studies comprising 1699 chronic myeloid leukemia patients were included in this analysis. The overall mean TFR rate at 24 months after entering TFR phase was 55% [95% confidence interval (CI) 0.51-0.58]. Trials with molecular criteria of MR4.5 or better for stopping TKI reported higher TFR rates than those of MR4.0 (57.2% vs. 50.5%). Trials with eligible criteria for at least 24 months of deep molecular response (DMR) duration demonstrated higher TFR rates than those for 18 or 12 months (60.2% vs. 49.9%). Our results suggest that TKI stopping trials with sufficient duration of DMR and molecular criteria of MR4.5 or better may account for approximately 60% of the TFR rate at 24 months after stopping TKI.
Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inducción de Remisión/métodos , Privación de Tratamiento/normas , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Several clinical trials that tested the efficacy of systemic treatments for advanced hepatocellular carcinoma (HCC) showed a tendency that patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection had different survival benefits from targeted agents. OBJECTIVE: The objective of this study was to assess the comparative efficacy of systemic targeted therapies according to HBV and HCV status in first-line and second- or later-line treatments for advanced HCC. METHODS: PubMed, EMBASE, Cochrane database, and meeting abstracts were searched through to January 2019. A Bayesian network meta-analysis was performed to estimate hazard ratios (HRs) for overall survival with 95% credible intervals (CrIs) and determine the ranking of the included regimens. RESULTS: Sixteen trials involving 6410 patients were included in the meta-analysis. In the first-line treatment setting, lenvatinib was the best agent for both HBV and HCV subgroups, presenting the most favorable HR versus sorafenib (HR 0.83, 95% CrI 0.68-1.01 and HR 0.91, 95% CrI 0.66-1.25, respectively), and was ranked as the best agent [surface under the cumulative ranking curve (SUCRA) value of 87% and 85%, respectively] among the included drugs. In second-line therapy, regorafenib showed the lowest HR versus placebo (HR 0.58, 95% CrI 0.41-0.82) in the HBV subgroup, whereas no agent was significantly more effective than placebo in the HCV subgroup. CONCLUSIONS: Compared with sorafenib, lenvatinib was more efficacious in the HBV subgroup than in the HCV subgroup, and the relative ranking of sorafenib in the HBV subgroup was lower than in the HCV subgroup. Each targeted agent reported to be the best by viral etiology and line of treatment could be carefully recommended in each subgroup.
Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/virología , Neoplasias Hepáticas/virología , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Metaanálisis en RedRESUMEN
PURPOSE: To investigate blood-based dynamic biomarkers that predict responses to anti-programmed cell death protein 1 (PD-1) therapy in solid tumors. EXPERIMENTAL DESIGN: Preplanned biomarker analysis was performed as part of a phase II clinical trial (NCT02607631) in patients with metastatic or refractory thymic epithelial tumors (TETs; n = 31) who received pembrolizumab. The biomarker was further tested in an independent cohort of prospectively recruited patients with metastatic non-small cell lung cancer (NSCLC) who received pembrolizumab or nivolumab (NSCLC cohort 1; n = 33) and validated in an independent cohort of patients with NSCLC (NSCLC cohort 2; n = 46). Peripheral blood samples were obtained immediately before treatment (D0) and 7 days after the first dose (D7) and analyzed using multi-color flow cytometry. RESULTS: A higher fold-change in the percentage of Ki-67+ cells among PD-1+CD8+ T cells 7 days after the first dose (Ki-67D7/D0) significantly predicted durable clinical benefit (DCB; P < 0.001) and prolonged progression-free survival (PFS; P = 0.027) in patients with TETs. Ki-67D7/D0 ≥ 2.8 was also associated with better DCB, PFS, and overall survival (OS) in NSCLC cohort 1 (all P < 0.05). Ki-67D7/D0 was subsequently validated in NSCLC cohort 2, and Ki-67D7/D0 ≥ 2.8 significantly predicted better DCB (P = 0.001), PFS (P = 0.002), and OS (P = 0.037). Ki-67D7/D0 had a low correlation with tumor PD-L1 expression and combining both factors did not improve the predictive power of Ki-67D7/D0. CONCLUSIONS: The proliferative response of peripheral blood PD-1+CD8+ T cells, measured as the fold-change in the percentage of Ki-67+ cells 7 days after treatment (Ki-67D7/D0), may be a useful surrogate biomarker for predicting the response and prognosis to anti-PD-1 therapy in solid tumors.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proliferación Celular/efectos de los fármacos , Femenino , Citometría de Flujo , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Neoplasias/diagnóstico , Neoplasias/mortalidad , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Curva ROC , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: While concerns regarding trastuzumab-related cardiac dysfunction (TRCD) in patients with breast cancer are increasing, there is a lack of evidence supporting the current recommendations for TRCD monitoring. We aimed to investigate the clinical predictors of TRCD in the adjuvant setting of human epidermal growth factor receptor 2-positive breast cancer patients. MATERIALS AND METHODS: From August 2003 to April 2016, consecutive 998 patients who were treated with adjuvant trastuzumab for breast cancer were retrospectively evaluated. TRCD was defined as a decrease ≥10% in left ventricular ejection fraction (LVEF), with a decline below the normal limit or symptomatic heart failure. RESULTS: Among 787 eligible patients who had complete data sets consisting of both baseline and follow-up assessment of left ventricular systolic function by echocardiography (mean age, 49.9±9.5 years), 58 (7.4%) developed TRCD. TRCD patients had lower baseline LVEF (63% [59-66] vs. 65% [61-68], p=0.016) and more frequently administered Adriamycin (98% vs. 89%, p=0.022) than those without TRCD. On follow-up echocardiography, a drop in LVEF ≥5% within the first 3 months was more frequent in TRCD patients (78.3% vs. 38.4%, p<0.001). Regardless of baseline LVEF and Adriamycin treatment, a drop in LVEF ≥5% within the first 3 months of trastuzumab administration was strongly associated with the development of TRCD (adjusted hazard ratio, 45.1[17.0-127.6], p<0.001). CONCLUSION: The overall incidence of TRCD was 7.4% in Asian breast cancer patients treated with adjuvant trastuzumab. A decline in LVEF ≥5% within the first 3 months of trastuzumab initiation was strongly associated with TRCD development in patients with breast cancer.
Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Neoplasias de la Mama/complicaciones , Volumen Sistólico , Trastuzumab/efectos adversos , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatología , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/mortalidad , Cardiotoxicidad , Comorbilidad , Femenino , Encuestas de Atención de la Salud , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Sistema de Registros , Factores de Riesgo , Trastuzumab/uso terapéutico , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/epidemiologíaRESUMEN
PURPOSE: The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). MATERIALS AND METHODS: We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles. RESULTS: A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms. CONCLUSION: The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino , Receptores ErbB/genética , Femenino , Humanos , Quimioterapia de Inducción , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Quimioterapia de Mantención , Masculino , Pemetrexed , Inhibidores de Proteínas Quinasas/uso terapéutico , Calidad de Vida , Retratamiento , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
PURPOSE: Limited treatment options exist for patients with thymic epithelial tumor (TET) whose disease progresses after platinum-based chemotherapy. We conducted a phase II study of pembrolizumab in patients with TET to evaluate its efficacy and safety. METHODS: Patients with histologically confirmed TET whose disease progressed after at least one line of platinum-based chemotherapy were eligible for the study. Patients were excluded if they had an active autoimmune disease requiring systemic treatment within the past year or documented history of clinically severe autoimmune disease. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until tumor progression or unacceptable toxicity. The primary objective of response rate was assessed every 9 weeks by investigators. RESULTS: Of 33 patients enrolled, 26 had thymic carcinoma and seven had thymoma. Of seven thymoma, two (28.6%; 95% CI, 8.2% to 64.1%) had partial response, and five (71.6%) had stable disease. Of 26 thymic carcinoma, five (19.2%; 95% CI, 8.5% to 37.9%) had partial response and 14 (53.8%) had stable disease. The median progression-free survival was 6.1 months for both groups. The most common adverse events of any grade included dyspnea (11; 33.3%), chest wall pain (10; 30.3%), anorexia (seven; 21.2%), and fatigue (seven; 21.2%). Five (71.4%) of seven patients with thymoma and four (15.4%) of 26 patients with thymic carcinoma reported grade ≥ 3 immune-related adverse events, including hepatitis (four; 12.1%), myocarditis (three; 9.1%), myasthenia gravis (two; 6.1%), thyroiditis (one; 3.0%), antineutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis (one; 3.0%), colitis (one; 3.0%), and subacute myoclonus (one; 3.0%). CONCLUSIONS: Pembrolizumab showed encouraging antitumor activity in patients with advanced TET. Given the high incidence of autoimmunity, additional studies are needed to identify those who can benefit from pembrolizumab without immune-related adverse events.