A plain language summary of the results from the phase 2b HERIZON-BTC-01 study of zanidatamab in participants with HER2-amplified biliary tract cancer

Biliary tract cancer; HER2-positive; ZanidatamabCáncer de las vías biliares; HER2 positivo; ZanidatamabCàncer de les vies biliars; HER2 positiu; ZanidatamabWhat is this summary about?: Researchers wanted to study whether the research drug zanidatamab could help people with a type of cancer called biliary tract cancer. In some people, biliary tract cancer cells make extra copies of a gene called HER2 (also called ERBB2). This is known as being HER2-amplified. Zanidatamab is an antibody designed to destroy cancer cells that have higher-than-normal HER2 protein or gene levels. Zanidatamab is currently under research and is not yet approved for any diseases. Participants in this phase 2b clinical study had tumors that were HER2-amplified and at the advanced or metastatic stage. Participants also had cancer which had become worse after previous chemotherapy or had side effects that were too bad to continue chemotherapy. They also had to meet other requirements to be enrolled. Researchers measured the amount of HER2 protein in the tumor samples of the participants who were enrolled. There were 80 participants with tumors that were both HER2 amplified and had higher-than-normal HER2 protein amounts (considered to be 'HER2-positive'). There were 7 participants with tumors that were HER2-amplified, but had little-to-no levels of the HER2 protein (considered to be 'HER2-low'). All participants in the study were treated with zanidatamab and no other cancer treatments once every 2 weeks. What are the key takeaways?: In the HER2-positive group, 33 of 80 (41%) participants had their tumors shrink by 30% or more of their original size. In half of these participants, their tumors did not grow for 13 months or longer. No participant in the HER2-low group had their tumors shrink by 30% or more. In total, 63 of 87 participants (72%) had at least one side effect believed to be related to zanidatamab treatment. Most side effects were mild or moderate in severity. No participant died from complications related to zanidatamab. Diarrhea was one of the more common side effects and was experienced by 32 of 87 participants (37%). Side effects related to receiving zanidatamab through the vein, such as chills, fever, or high blood pressure, were experienced by 29 of 87 participants (33%). What are the conclusions reported by the researchers?: The results of this study support the potential for zanidatamab as a new therapy for people with HER2-positive biliary tract cancer after they had already received chemotherapy. More research is occurring to support these results.Clinical Trial Registration: NCT04466891 (HERIZON-BTC-01 study).Funding and the drug for this study were provided by the following pharmaceutical companies: Zymeworks, Jazz Pharmaceuticals, and BeiGene

Systemic chemotherapy for treatment of advanced small bowel adenocarcinoma with prognostic factor analysis: retrospective study

<p>Abstract</p> <p>Background</p> <p>We sought to evaluate prognostic factors affecting overall survival (OS), and to investigate the role of palliative chemotherapy using propensity score-based weighting, in patients with advanced small bowel adenocarcinoma (SBA).</p> <p>Methods</p> <p>Data from a total of 91 patients diagnosed with advanced SBA at the Asan Medical Center between January 1989 and December 2009 were retrospectively analyzed. Patients were split into two groups, those who did and did not receive palliative chemotherapy.</p> <p>Results</p> <p>Overall, 81 patients (89.0%) died, at a median survival time of 6.6 months (95% confidence interval [CI], 5.5 - 7.5 months). The 40 patients receiving chemotherapy showed overall response and disease control rates of 11.1% and 37.0%, respectively, with OS and progression-free survival (PFS) of 11.8 months (95% CI, 4.6 - 19.0 months) and 5.7 months (95% CI, 3.5 - 8.0 months), respectively. The 41 patients who did not receive chemotherapy had an OS of 4.1 months (95% CI, 3.1 - 5.1 months) and a PFS of 1.3 months (95% CI, 0.8 - 1.7 months). Multivariate analysis showed that lack of tumor resection, non-prescription of chemotherapy, liver metastasis, and intra-abdominal lymph node metastasis, were all independently associated with poor survival outcomes. After inverse probability of treatment weighting (IPTW) adjustment, the group that did not receive chemotherapy was at a significantly higher risk of mortality (HR 3.44, 95% CI 2.03 - 5.83, p < 0.001) than were patients receiving chemotherapy.</p> <p>Conclusion</p> <p>Palliative chemotherapy may improve survival outcomes in patients with advanced SBA.</p

Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review

© 2016 Background Fractional exhaled nitric oxide (FENO) is a safe and convenient test for assessing T H 2 airway inflammation, which is potentially useful in the management of patients with chronic cough. Objective To summarize the current evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough. Methods A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of FENO (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 × 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Results We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from abou t 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency. Conclusions We did not find strong evidence to support the use of FENO tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence

The Effect of Doxycycline on PMA-Induced MUC5B Expression via MMP-9 and p38 in NCI-H292 Cells

ObjectivesDoxycycline is commonly used in medicine for its bacteriostatic antimicrobial properties. Recent studies have reported that doxycycline also has anti-inflammatory effects. Matrix metalloproteinase (MMP)-9 has been found to be involved in the physiological and pathological process of inflammatory airway disease. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, is known to stimulate the expression of MMP and mucin genes in the airway and intestinal epithelial cells. Therefore, the effects and signal pathways of doxycycline on PMA-induced MUC5B expression dependent MMP-9 in human airway epithelial cells were investigated.MethodsIn human NCI-H292 airway epithelial cells, MUC5B and MMP-9 mRNA expression, MUC5B protein expression, and MMP-9 protein activity after the treatment with PMA, MMP-9 or doxycycline were determined by reverse transcriptase-polymerase chain reaction, enzyme immunoassay, gelatin zymography, and Western blot analysis.ResultsPMA increased MMP-9 and MUC5B expression. MMP-9 increased MUC5B expression. Doxycycline inhibited PMA-induced MUC5B expression, and PMA-induced MMP-9 mRNA expression and protein activity. Doxycycline inhibited phosphorylation of p38 induced by PMA and MMP-9.ConclusionThe results of this study suggest that doxycycline inhibited PMA-induced MUC5B mRNA expression and protein production through the MMP-9 and p38 pathways in human NCI-H292 airway epithelial cells