RESUMO
Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Colorretais , Combinação de Medicamentos , Pirrolidinas , Timina , Trifluridina , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Trifluridina/uso terapêutico , Trifluridina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pirrolidinas/uso terapêutico , Pirrolidinas/administração & dosagem , Metástase Neoplásica , Intervalo Livre de Progressão , Uracila/análogos & derivados , Uracila/uso terapêutico , Uracila/administração & dosagem , Resistencia a Medicamentos AntineoplásicosRESUMO
In retinopathy of prematurity (ROP) type I, the use of intravitreal bevacizumab (IVB), which is an inhibitor of endothelial growth factor (VEGF), has become popular despite not being a therapy approved by regulatory agencies. However, IVB has shown positive effects in halting disease progression at lower costs compared to other anti-VEGF therapies (ranibizumab or aflibercept). In this report, we present the experience during the treatment with IVB of 102 Colombian children with ROP type I, with a success rate of 98% (100). Complications occurred in 3.9% (4). Finally, we conclude that a single dose of IVB is an effective therapy for the management of ROP type I, with a lower risk of complications and retreatment.
Assuntos
Inibidores da Angiogênese , Bevacizumab , Injeções Intravítreas , Retinopatia da Prematuridade , Humanos , Retinopatia da Prematuridade/tratamento farmacológico , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Recém-Nascido , Masculino , Feminino , Colômbia , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
BACKGROUND: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. METHODS: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. RESULTS: From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. CONCLUSIONS: Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT01733628.
Assuntos
Bevacizumab , Neoplasias da Mama , Neoplasias Colorretais , Hipertensão , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Hipertensão/induzido quimicamente , Estudos Prospectivos , Idoso , Masculino , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão , Metilação de DNARESUMO
PURPOSE: To investigate the clinical benefits of the co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy. METHODS: Patients who underwent vitrectomy for proliferative dia-betic retinopathy complications were preoperatively given in-travitreal injection with either bevacizumab and tissue plasminogen activator (Group 1) or bevacizumab alone (Group 2). Primary outcomes were surgery time and number of intraoperative iatrogenic retinal breaks. Secondary outcomes included changes in the best-corrected visual acuity and postoperative complications at 3 months postoperatively. RESULTS: The mean surgery time in Group 1 (52.95 ± 5.90 min) was significantly shorter than that in Group 2 (79.61 ± 12.63 min) (p<0.001). The mean number of iatrogenic retinal breaks was 0.50 ± 0.59 (0-2) in Group 1 and 2.00 ± 0.83 (0-3) in Group 2 (p<0.001). The best-corrected visual acuity significantly improved in both groups (p<0.001). One eye in each group developed retinal detachment. CONCLUSION: Preoperative co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy shortens the surgery time and reduces the number of intraoperative iatrogenic retinal breaks.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Perfurações Retinianas , Humanos , Ativador de Plasminogênio Tecidual/uso terapêutico , Bevacizumab/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/cirurgia , Vitrectomia , Doença IatrogênicaRESUMO
OBJECTIVE: This study aimed to determine whether the combined use of bevacizumab could improve overall survival (OS) in patients with brain metastasis (BM), epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) undergoing cerebral radiotherapy. MATERIALS AND METHODS: A total of 237 patients with EGFR-mutant lung adenocarcinoma and BM met the inclusion criteria for this retrospective study, including 102 patients in the bevacizumab treatment group and 135 in the non-bevacizumab group. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to identify EGFR-mutated BM prognostic factors for these patients. RESULTS: At the end of the last follow-up period, 176 patients (74.3%) had died, and the median overall survival (OS) was 34.2 months. We observed a significant difference in the median OS between the bevacizumab and non-bevacizumab groups (45.8 months vs 30.0 months, P < 0.0001). Among the 178 (75.1%) patients who received cerebral radiotherapy, the median OS of patients in the bevacizumab + cerebral radiotherapy group was 45.8 months versus 32.0 months in the non-bevacizumab + cerebral radiotherapy group, respectively (P = 0.0007). Patients treated with bevacizumab after cerebral radiotherapy had a longer median OS than patients treated with bevacizumab before cerebral radiotherapy (59.4 months vs 33.7 months, P = 0.0198). In the univariate analysis, smoking status, Lung-molGPA scores, and bevacizumab therapy showed correlations (HR = 1.450, P = 0.045; HR = 0.700, P = 0.023; HR = 0.499, P < 0.001). Multivariate analysis showed that bevacizumab therapy alone (hazard ratio [HR] = 0.514; P < 0.001) was independently associated with improved OS. CONCLUSION: In patients with BM from EGFR-mutated NSCLC, cerebral radiotherapy with bevacizumab markedly improved OS. This improvement was more evident after cerebral radiotherapy.
Assuntos
Adenocarcinoma de Pulmão , Bevacizumab , Neoplasias Encefálicas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Humanos , Bevacizumab/uso terapêutico , Masculino , Feminino , Receptores ErbB/genética , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Prognóstico , Idoso , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/radioterapia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/terapia , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adenocarcinoma/secundário , Irradiação Craniana/métodos , Taxa de Sobrevida , Idoso de 80 Anos ou mais , Estimativa de Kaplan-Meier , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , SeguimentosRESUMO
OBJECTIVE: To compare efficacy and safety profile of subretinal aflibercept, ranibizumab, and bevacizumab in the context of pars plana vitrectomy, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage (SMH) due to naïve neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective interventional cohort study. PARTICIPANTS: 123 eyes of 123 patients treated with subretinal aflibercept (n = 41, 33%), ranibizumab (n = 41,33%), and bevacizumab (n = 41, 33%). METHODS: Review of electronic medical records for best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) at baseline and 24 months after treatment. MAIN OUTCOME MEASURES: BCVA, CST, and number of intravitreal anti VEGF over 24 months. RESULTS: Mean age of patients was 80.5 ± 5.5 years, 43.9% were female. Mean time from symptom onset until surgery was 1.1 days (range 0-3 days). In all cases, the SMH did not reach the arcades. CST at baseline was 627 ± 140 µ, 739 ± 54 µ, and 793 ± 93 µ (p = 0.0001) for aflibercept, ranibizumab, or bevacizumab, respectively. Baseline BCVA (logMAR) was 0.65 ± 0.13, 0.69 ± 0.96, and 0.74 ± 0.81 (p = 0.0041) for aflibercept, ranibizumab, and bevacizumab, respectively. All three groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no statistically significant difference at the final BCVA (p = 0.789). The mean number of anti VEGF given during follow-up period was 5.2 ± 0.81, 4.4 ± 0.63, and 5.5 ± 0.95 (p = 0.0001) for aflibercept, ranibizumab, and bevacizumab, respectively. CONCLUSION: This study shows that aflibercept, ranibizumab, and bevacizumab in a subretinal manner in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage secondary to naïve nAMD work with the same efficacy and safety profile.
Assuntos
Inibidores da Angiogênese , Ranibizumab , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Ranibizumab/uso terapêutico , Bevacizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Estudos Retrospectivos , Estudos de Coortes , Resultado do Tratamento , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Hemorragia Retiniana/tratamento farmacológico , Hemorragia Retiniana/etiologia , Injeções IntravítreasRESUMO
ABSTRACT Objective: To characterize the effectiveness of anti-vascular endothelial growth factor drugs in exudative age-related macular degeneration. Methods: Retrospective longitudinal study of 54 patients with age-related macular degeneration receiving bevacizumab or aflibercept. Demographic data, visual acuity, and central retinal thickness measurements were collected. Improvement/stability of visual acuity and reduction in retinal thickness configured satisfactory responses. Results: Among the 60 eyes studied, there was no difference (p = 0.262) in satisfactory response when using bevacizumab (48.5%) or aflibercept (63.0%). Snellen's visual acuity, letter gain, and retinal thickness showed improvement or maintenance in 55.0%, 32.8%, and 78.3% of cases, respectively. The percentage of improvement/maintenance was higher in eyes with an initial visual acuity of < Snellen 20/400 (70.0% versus 40.0%; p = 0.002). Conclusion: A higher percentage of improvement/stabilization of visual acuity and macular thickness was observed in patients with age-related macular degeneration, with better response in patients with visual acuity worse than Snellen 20/400.
RESUMO Objetivo: Caracterizar a efetividade de medicamentos antifactor de crescimento endotelial vascular na degeneração macular relacionada à idade exsudativa. Métodos: Estudo longitudinal retrospectivo em 54 pacientes com degeneração macular relacionada à idade que usaram bevacizumab ou aflibercept. Foram coletados dados demográficos, da acuidade visual e da espessura central da retina. Melhora/estabilidade da acuidade visual e redução da espessura configuraram respostas satisfatórias. Resultados: Entre 60 olhos estudados, não houve diferença (p = 0,262) de acordo com o uso de bevacizumab (48,5%) ou aflibercept (63,0%). Acuidade visual segundo Snellen, ganho de letras e espessura retiniana demonstraram melhora ou estabilidade em 55,0%, 32,8% e 78,3% dos casos, respectivamente. Entre os olhos com acuidade visual inicial < 20/400, o percentual de melhora/estabilidade foi superior (70,0% versus 40,0%; p = 0,002). Conclusão: Em pacientes com degeneração macular relacionada à idade, foi percebida uma maior proporção de melhora ou estabilização da acuidade visual e espessura macular, com melhor resposta entre os pacientes com visão pior que 20/400.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Degeneração Macular/tratamento farmacológico , Acuidade Visual , Estudos Retrospectivos , Estudos de Coortes , Estudos Longitudinais , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/diagnóstico , Injeções Intravítreas , Degeneração Macular/diagnósticoAssuntos
Telangiectasia Hemorrágica Hereditária , Humanos , Bevacizumab/uso terapêutico , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Resultado do Tratamento , Doença CrônicaRESUMO
INTRODUCTION: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab. METHODS: This is a randomized, phase II, multicenter study evaluating carboplatin, pemetrexed, bevacizumab with and without atezolizumab in 117 patients with stage IV nonsquamous NSCLC. Randomization is 2 to 1 favoring the atezolizumab containing arm. Eligible patients include: 1) those with tumors with sensitizing EGFR alterations in exons 19 or 21 or 2) patients who have never smoked and have wild-type tumors (ie, no EGFR, ALK or ROS1 alterations). Patients are defined as having never smoked if they have smoked less than 100 cigarettes in a lifetime. Patients with EGFR-mutated tumors must have disease progression or intolerance to prior tyrosine kinase inhibitor (TKI) therapy. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate, duration of response, and time to response. CONCLUSION: This phase II trial is accruing patients at U.S. sites through the National Comprehensive Cancer Network (NCCN). The trial opened in August 2019 and accrual is expected to be completed in the Fall of 2024.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carboplatina/uso terapêutico , Pemetrexede/uso terapêutico , Bevacizumab/uso terapêutico , Antígeno B7-H1/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fumaça , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Receptores ErbB/genética , Receptores ErbB/uso terapêutico , Mutação/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologiaRESUMO
INTRODUCTION: The second-line chemotherapy in metastatic colorectal cancer (mCRC) with FOLFIRI-aflibercept demonstrated an increase in survival compared with FOLFIRI in patients previously treated with oxaliplatin-based regimens. Few data are available in patients treated previously with bevacizumab. Our objective is to evaluate the efficacy and safety of FOLFIRI-aflibercept in second-line treatment in patients who have previously received bevacizumab. PATIENTS AND METHODS: This is a observational, retrospective study of patients with mCRC treated with FOLFIRI-aflibercept in 2nd line in eight hospitals in the Valencian Community. Survival, response, and toxicity were analyzed. RESULTS: 122 patients with a median age of 61 years were included. 89% of patients had PS 0-1. The median of PFS (progression free survival) and OS (overall survival) was 5.45 (95% CI 4.74-6.15 months) and 10.15 (95% CI 7.47-12.82 months), respectively. Disease control rate 59.8%. The most common grade 3-4 adverse events were neutropenia (13,1%) and asthenia (9%). The presence of hypertension during treatment with FOLFIRI-aflibercept was associated with a survival benefit. Median of OS was 14.45 (95% CI 11.58-17.32) in patients with hypertension vs 7.78 (95% CI 5.02-10.54) in patients without hypertension (p = .001). Our results suggest that the presence of PS 0, primary tumor surgery, metachronous metastases, and the presence of only 1 metastatic location, are favorable prognostic factors associated with better OS. CONCLUSIONS: Our results confirm the value of maintaining angiogenesis inhibition with FOLFIRI-aflibercept in mCRC after progression to a first-line treatment with bevacizumab. The development of hypertension during treatment is a possible predictive marker of response.