Background: HER2 is an actionable target in metastatic colorectal cancer. We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer. Methods: MOUNTAINEER is a global, open-label, phase 2 study that enrolled patients aged 18 years and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites (clinics and hospitals) in five countries (Belgium, France, Italy, Spain, and the USA). Initially, the study was designed as a single-cohort study, which was expanded following an interim analysis to include more patients. Initially, patients were given tucatinib (300 mg orally twice daily) plus intravenous trastuzumab (8 mg/kg as an initial loading dose, then 6 mg/kg every 21 days; cohort A) for the duration of treatment (until progression), and after expansion, patients were randomly assigned (4:3), using an interactive web response system and stratified by primary tumour location, to either tucatinib plus trastuzumab (cohort B) or tucatinib monotherapy (cohort C). The primary endpoint was confirmed objective response rate per blinded independent central review (BICR) for cohorts A and B combined and was assessed in patients in the full analysis set (ie, patients with HER2-positive disease who received at least one dose of study treatment). Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT03043313, and is ongoing. Findings: Between Aug 8, 2017, and Sept 22, 2021, 117 patients were enrolled (45 in cohort A, 41 in cohort B, and 31 in cohort C), of whom 114 patients had locally assessed HER2-positive disease and received treatment (45 in cohort A, 39 in cohort B, and 30 in cohort C; full analysis set), and 116 patients received at least one dose of study treatment (45 in cohort A, 41 in cohort B, and 30 in cohort C; safety population). In the full analysis set, median age was 56·0 years (IQR 47–64), 66 (58%) were male, 48 (42%) were female, 88 (77%) were White, and six (5%) were Black or African American. As of data cutoff (March 28, 2022), in 84 patients from cohorts A and B in the full analysis set, the confirmed objective response rate per BICR was 38·1% (95% CI 27·7–49·3; three patients had a complete response and 29 had a partial response). In cohorts A and B, the most common adverse event was diarrhoea (55 [64%] of 86), the most common grade 3 or worse adverse event was hypertension (six [7%] of 86), and three (3%) patients had tucatinib-related serious adverse events (acute kidney injury, colitis, and fatigue). In cohort C, the most common adverse event was diarrhoea (ten [33%] of 30), the most common grade 3 or worse adverse events were increased alanine aminotransferase and aspartate aminotransferase (both two [7%]), and one (3%) patient had a tucatinib-related serious adverse event (overd
{"title":"Kolorektales Karzinom: Wirksamkeit der Tucatinib-Trastuzumab-Kombination bei HER2-positivem Tumor","authors":"Kia Homayounfar","doi":"10.1159/000533180","DOIUrl":"https://doi.org/10.1159/000533180","url":null,"abstract":"Background: HER2 is an actionable target in metastatic colorectal cancer. We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer. Methods: MOUNTAINEER is a global, open-label, phase 2 study that enrolled patients aged 18 years and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites (clinics and hospitals) in five countries (Belgium, France, Italy, Spain, and the USA). Initially, the study was designed as a single-cohort study, which was expanded following an interim analysis to include more patients. Initially, patients were given tucatinib (300 mg orally twice daily) plus intravenous trastuzumab (8 mg/kg as an initial loading dose, then 6 mg/kg every 21 days; cohort A) for the duration of treatment (until progression), and after expansion, patients were randomly assigned (4:3), using an interactive web response system and stratified by primary tumour location, to either tucatinib plus trastuzumab (cohort B) or tucatinib monotherapy (cohort C). The primary endpoint was confirmed objective response rate per blinded independent central review (BICR) for cohorts A and B combined and was assessed in patients in the full analysis set (ie, patients with HER2-positive disease who received at least one dose of study treatment). Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT03043313, and is ongoing. Findings: Between Aug 8, 2017, and Sept 22, 2021, 117 patients were enrolled (45 in cohort A, 41 in cohort B, and 31 in cohort C), of whom 114 patients had locally assessed HER2-positive disease and received treatment (45 in cohort A, 39 in cohort B, and 30 in cohort C; full analysis set), and 116 patients received at least one dose of study treatment (45 in cohort A, 41 in cohort B, and 30 in cohort C; safety population). In the full analysis set, median age was 56·0 years (IQR 47–64), 66 (58%) were male, 48 (42%) were female, 88 (77%) were White, and six (5%) were Black or African American. As of data cutoff (March 28, 2022), in 84 patients from cohorts A and B in the full analysis set, the confirmed objective response rate per BICR was 38·1% (95% CI 27·7–49·3; three patients had a complete response and 29 had a partial response). In cohorts A and B, the most common adverse event was diarrhoea (55 [64%] of 86), the most common grade 3 or worse adverse event was hypertension (six [7%] of 86), and three (3%) patients had tucatinib-related serious adverse events (acute kidney injury, colitis, and fatigue). In cohort C, the most common adverse event was diarrhoea (ten [33%] of 30), the most common grade 3 or worse adverse events were increased alanine aminotransferase and aspartate aminotransferase (both two [7%]), and one (3%) patient had a tucatinib-related serious adverse event (overd","PeriodicalId":477056,"journal":{"name":"Karger Kompass","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136078903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been increasingly applied in the treatment of retinal neovascular diseases. Concerns have arisen that these intravitreal agents may be associated with a potential risk of arterial thromboembolic (ATE) events. We conducted a retrospective, nationwide population-based cohort study to analyze the risks for ATE events in patients receiving intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA). Data (2011–2018) were obtained from Taiwan’s National Health Insurance Research Database. Cox proportional-hazards model was used to identify the risk factors for ATEs. Of the total 3,469 patients, 1393 and 2076 patients received IVR and IVA, respectively. In our result, 38 ATEs occurred within 6 months after IVR or IVA. The risk of ATEs was lower in patients receiving IVR than in those receiving IVA (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.11–0.66). Patients with coronary artery disease (CAD) exhibited a higher risk of ATEs than did those without CAD (aHR, 3.47; 95% CI, 1.41–8.53). The risk of ATEs was higher in patients with an event of acute myocardial infarction (AMI) or ischemic stroke (IS) within 6 months prior to index IVI than in those without recent AMI/IS events (aHR, 23.8; 95% CI, 7.35–77.2 and IS: aHR, 290.2; 95% CI, 103.1–816.4). In conclusion, compared with IVA, IVR was associated with a lower risk of ATEs. When strategies for anti-VEGF agents are devised, risk factors, such as CAD and a history of AMI or IS within 6 months should be considered. Further large-scale studies are warranted to elucidate the safety of anti-VEGF injections.
{"title":"Neues von der Anti-VEGF-A-Therapie","authors":"Olaf Strauß","doi":"10.1159/000534606","DOIUrl":"https://doi.org/10.1159/000534606","url":null,"abstract":"Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been increasingly applied in the treatment of retinal neovascular diseases. Concerns have arisen that these intravitreal agents may be associated with a potential risk of arterial thromboembolic (ATE) events. We conducted a retrospective, nationwide population-based cohort study to analyze the risks for ATE events in patients receiving intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA). Data (2011–2018) were obtained from Taiwan’s National Health Insurance Research Database. Cox proportional-hazards model was used to identify the risk factors for ATEs. Of the total 3,469 patients, 1393 and 2076 patients received IVR and IVA, respectively. In our result, 38 ATEs occurred within 6 months after IVR or IVA. The risk of ATEs was lower in patients receiving IVR than in those receiving IVA (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.11–0.66). Patients with coronary artery disease (CAD) exhibited a higher risk of ATEs than did those without CAD (aHR, 3.47; 95% CI, 1.41–8.53). The risk of ATEs was higher in patients with an event of acute myocardial infarction (AMI) or ischemic stroke (IS) within 6 months prior to index IVI than in those without recent AMI/IS events (aHR, 23.8; 95% CI, 7.35–77.2 and IS: aHR, 290.2; 95% CI, 103.1–816.4). In conclusion, compared with IVA, IVR was associated with a lower risk of ATEs. When strategies for anti-VEGF agents are devised, risk factors, such as CAD and a history of AMI or IS within 6 months should be considered. Further large-scale studies are warranted to elucidate the safety of anti-VEGF injections.","PeriodicalId":477056,"journal":{"name":"Karger Kompass","volume":"2014 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135104819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: GCA is the commonest primary systemic vasculitis in adults, with significant health economic costs and societal burden. There is wide variation in access to secondary care GCA services, with 34% of hospitals in England not having any formal clinical pathway. Quality standards provide levers for change to improve services. Methods: The multidisciplinary steering committee were asked to anonymously put forward up to five aspects of service essential for best practice. Responses were qualitatively analysed to identify common themes, subsequently condensed into domain headings, and ranked in order of importance. Quality standards and metrics for each domain were drafted, requiring a minimum 75% agreement. Results: 13 themes were identified from the initial suggestions. Nine quality standards with auditable metrics were developed from the top 10 themes. Patient Access, glucocorticoid use, pathways, ultrasonography, temporal artery biopsy, PET scan access, rheumatology/ophthalmology expertise, education, multidisciplinary working have all been covered in these quality standards. Access to care is a strand that has run through each of the developed standards. An audit tool was developed as part of this exercise.
{"title":"Empfehlungen für die interdisziplinäre Betreuung von Patienten mit Riesenzellarteriitis: «Giant Cell Arteritis Hospital Quality Standards» (GHOST)","authors":"Christoph Tappeiner","doi":"10.1159/000534122","DOIUrl":"https://doi.org/10.1159/000534122","url":null,"abstract":"<b>Objective:</b> GCA is the commonest primary systemic vasculitis in adults, with significant health economic costs and societal burden. There is wide variation in access to secondary care GCA services, with 34% of hospitals in England not having any formal clinical pathway. Quality standards provide levers for change to improve services. <b>Methods:</b> The multidisciplinary steering committee were asked to anonymously put forward up to five aspects of service essential for best practice. Responses were qualitatively analysed to identify common themes, subsequently condensed into domain headings, and ranked in order of importance. Quality standards and metrics for each domain were drafted, requiring a minimum 75% agreement. <b>Results:</b> 13 themes were identified from the initial suggestions. Nine quality standards with auditable metrics were developed from the top 10 themes. Patient Access, glucocorticoid use, pathways, ultrasonography, temporal artery biopsy, PET scan access, rheumatology/ophthalmology expertise, education, multidisciplinary working have all been covered in these quality standards. Access to care is a strand that has run through each of the developed standards. An audit tool was developed as part of this exercise.","PeriodicalId":477056,"journal":{"name":"Karger Kompass","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135211706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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