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BACKGROUND: Advanced systemic mastocytosis (advSM) is characterized by presence of the KIT D816V mutation and pathologic accumulation of neoplastic mast cells (MCs) in various tissues, leading to severe symptoms and organ damage (eg, cytopenias, liver dysfunction, portal hypertension, malabsorption, and weight loss). Treatment with midostaurin, an orally active multikinase/KIT inhibitor now approved for advSM in the United States and the European Union, resulted in a high rate of response accompanied by reduced MC infiltration of the bone marrow and lowered serum tryptase level. OBJECTIVE: We aimed to determine whether midostaurin improves health-related quality of life (QOL) and MC mediator-related symptoms in patients with advSM. METHODS: In 116 patients with systemic mastocytosis (89 patients with advSM fulfilling the strict inclusion criteria of the D2201 study [ClinicalTrials.gov identifier NCT00782067]), QOL and symptom burden were assessed during treatment with midostaurin by using the 12-Item Short-Form Health Survey (SF-12) and the Memorial Symptom Assessment Scale patient-reported questionnaires, respectively. MC mediator-related symptoms were evaluated by using a specific physician-reported questionnaire. RESULTS: Over the first 6 cycles of treatment with midostaurin (ie, 6 months), patients experienced significant improvements in total SF-12 and Memorial Symptom Assessment Scale scores, as well as in subscores of each instrument. These improvements were durable during 36 months of follow-up. Similarly, we found substantial improvements (67%-100%) in all MC mediator-related symptoms. CONCLUSION: QOL and MC mediator-related symptoms significantly improve with midostaurin treatment in patients with advSM (ClinicalTrials.gov identifier, NCT00782067).
Subject(s)
Mastocytosis, Systemic/drug therapy , Protein Kinase Inhibitors/therapeutic use , Staurosporine/analogs & derivatives , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Male , Mast Cells/pathology , Middle Aged , Quality of Life , Staurosporine/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) has evolved dramatically with the approval of immuno-oncology (IO) and targeted therapies (TTs). Insights on the patient experience with these therapies and their impacts are lacking. Health-related social media has been increasingly used by patients to share their disease and treatment experiences, thus representing a valuable source of real-world data to understand the patient's voice and uncover potential unmet needs. OBJECTIVE: This study aimed to describe the experiences of patients with NSCLC as reported in discussions posted on lung cancer-specific social media with respect to their disease symptoms and associated impacts. METHODS: Publicly available posts (2010-2019) were extracted from selected lung cancer- or NSCLC-specific websites. Social media users (patients and caregivers posting on these websites) were stratified by metastatic- and adjuvant-eligible subgroups and treatment received using natural language processing (NLP) and machine learning methods. Automated identification of symptoms was conducted using NLP. Qualitative data analysis (QDA) was conducted on random samples of posts mentioning pain-related, fatigue-related, respiratory-related, or infection-related symptoms to capture the patient experience with these and associated impacts. RESULTS: Overall, 1724 users (50,390 posts) and 574 users (4531 posts) were included in the metastatic group and adjuvant group, respectively. Among users in the metastatic group, pain, discomfort, and fatigue were the most commonly mentioned symptoms (49.7% and 39.6%, respectively), and in the QDA (258 posts from 134 users), the most frequent impacts related to physical impairments, sleep, and eating habits. Among users in the adjuvant group, pain, discomfort, and respiratory symptoms were the most commonly mentioned (44.8% and 23.9%, respectively), and impacts identified in the QDA (154 posts from 92 users) were mostly related to physical functioning. CONCLUSIONS: Findings from this exploratory observational analysis of social media among patients and caregivers informed the lived experience of NSCLC in the era of novel therapies, shedding light on most reported symptoms and their impacts. These findings can be used to inform future research on NSCLC treatment development and patient management.
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Introduction: BRAF mutations are rare in patients with NSCLC, and treatment options are limited. Dabrafenib plus trametinib (dab-tram) was approved for BRAFV600-mutated advanced NSCLC (aNSCLC), based on results from a phase 2 study (NCT01336634). This retrospective analysis compared the effectiveness of dab-tram, based on previously reported clinical trial data, versus real-world standard of care in patients with BRAF-mutated aNSCLC. Methods: Real-world cohorts were derived from a deidentified real-world database (2011-2020) and included patients with BRAF-mutated aNSCLC receiving first-line platinum-based chemotherapy (PBC), first-line immune checkpoint inhibitors (ICIs) plus PBC, or second-line ICIs. Weighting by odds was used to estimate the average treatment effect of the treated. Results: For first-line dab-tram versus PBC, the hazard ratio (HR; 95% confidence interval) for death in unweighted and weighted analyses was 0.65 (0.39-1.1) and 0.51 (0.29-0.92; p = 0.03), respectively; unweighted and weighted median overall survival was 17.3 (12.3-40.2) versus 14.5 (9.2-19.6) months and 17.3 (14.6-not reached) versus 9.7 (6.4-19.6) months, respectively. Hazard ratio of death in unweighted and weighted analyses was 0.56 (0.29-1.1) and 0.57 (0.28-1.17), respectively, with first-line dab-tram versus PBC plus ICI, and 0.65 (0.39-1.07) and not reported (Cox proportional-hazards assumption violated), respectively, with second-line dab-tram versus ICI. Conclusions: In this indirect comparison in patients with BRAF-mutated aNSCLC, the risk of death was lower and median overall survival was longer with first-line dab-tram versus PBC. In analyses of dab-tram versus first-line PBC plus ICI or second-line ICI, sample sizes were small and findings were inconclusive with overlapping confidence intervals. Despite some limitations, the study provides useful data for this rare patient population.
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Background More and more information about complementary and integrative medicine is becoming available, especially among cancer patients. However, little is known about the use of herbal medicine by patients with gynecologic cancers. This study aimed to assess the use of herbal products by gynecologic cancer patients compared with healthy controls. Methods This cross-sectional study was conducted at the Department for Gynecology and Obstetrics of Erlangen University Hospital and included 201 patients with gynecologic cancer and 212 healthy controls. Use of herbal medicines was evaluated using a standardized questionnaire. Medical information on cancer patients was collected from hospital records. Group comparisons were done using a logistic regression model. Risk ratios were assessed using a Poisson regression model. Results Gynecologic cancer patients used herbal medicine significantly less often than healthy persons. 69% of gynecologic cancer patients and 81% of healthy participants reported using herbal products. 40% of cancer patients and 56% of healthy persons reported using plants for medicinal purposes. Motives of cancer patients for using herbal medicine included treatment of cancer-related symptoms. The major source of information for both groups was family and friends. Conclusions Although herbal medicine was used less by patients with gynecologic cancer, herbal products were used by both cancer patients and healthy individuals. To provide cancer patients with optimal therapy, oncologists should be informed about the herbal products used by their patients as this will allow them to take their patients' self-medication with herbal medicine into account. Counseling by oncologists on the use of herbal medicine should be encouraged.
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Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI]) = 0.64 [0.47-0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value = 0.003). OS did not differ significantly, with a HR of 0.82 [0.54-1.27] for ceritinib compared to crizotinib.Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Crizotinib/administration & dosage , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Sulfones/administration & dosage , Aged , Anaplastic Lymphoma Kinase/antagonists & inhibitors , Brain Neoplasms/secondary , Female , Humans , Male , Middle Aged , Progression-Free Survival , Proportional Hazards ModelsABSTRACT
BACKGROUND: Rotavirus gastroenteritis (RVGE) is a frequent disease in young children. The recommended German paediatric immunisation schedule does not currently include rotavirus vaccination. A lack of economic data on the impact of routine vaccination is stated as one of the reasons. As a result, the current coverage rate is low, around 26%. This study investigated whether rotavirus vaccination using the two-dose rotavirus vaccine RIX4414 (Rotarix®, GlaxoSmithKline Vaccines) would be a cost-saving intervention from the perspective of the statutory health insurance (SHI) in Germany. OBJECTIVE: The objective of the study was to analyse health outcomes (number of RVGE cases and hospitalisations prevented) and the associated cost to the SHI when comparing 100% rotavirus vaccination with no vaccination in Germany. METHODS: A Markov cohort model simulated the number of RVGE events and related costs in a German birth cohort over the first 60 months of life with current disease management. The model compared an unvaccinated cohort with a fully vaccinated cohort. Vaccine efficacy data from international clinical trials were combined with German-specific epidemiological and cost data. Results were tested using extensive sensitivity analyses. RESULTS: Full vaccination of a birth cohort against rotavirus disease would be expected to prevent 82% of RVGE cases, reducing RVGE frequency from 28 to 5 events per 100 children in the birth cohort up to age 5 years. The estimated cost reduction with vaccination for that period is predicted to be 9.2 million with 100% coverage (6.9 million with 75% coverage), mainly due to reductions in SHI reimbursement for productivity losses, hospital stays and visits to office-based physicians due to the vaccine's efficacy against severe disease. CONCLUSIONS: Routine rotavirus vaccination in Germany would reduce the number of hospitalised and outpatient cases. The associated investment could be fully offset by costs avoided in hospital stays, physician visits and SHI reimbursement of productivity losses. Sensitivity analysis indicated that vaccination would be cost-saving in 95% of simulations. Incremental cost was observed only under extreme conditions, especially when the time spent at home due to rotavirus disease was low or when vaccine efficacy against severe disease was heavily decreased.
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This study estimated the impact of routine vaccination of infants with a new 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on health outcomes and costs across the entire population in Canada, Germany, Mexico, and Norway. A compartmental, static model with a 1-year time period for a steady-state population that allowed for the incorporation of direct and indirect (i.e., herd immunity and serotype replacement) vaccine effects across all age groups was used. Cases of disease prevented, deaths prevented, life-years gained, quality-adjusted life-years gained, and incremental costs in the steady-state year were calculated for PHiD-CV compared with 7-valent pneumococcal conjugate vaccine (PCV-7). A short-term analysis was also conducted to estimate the incremental difference in disease and cost outcomes for the two vaccines within the first 10 years. All costs were in 2008 local currency. In all four countries, the model estimated that PHiD-CV prevented more cases of disease, prevented more deaths, and resulted in more life-years and quality-adjusted life-years compared with PCV-7 in both the short term and the steady-state year. Assuming price parity for the vaccines, the model projected that routine vaccination with PHiD-CV resulted in lower costs compared with PCV-7 in both the short term and the steady-state year. Scenario analysis showed the incremental cost savings for PHiD-CV compared with PCV-7 in the steady-state year were sensitive to assumptions regarding duration of vaccine efficacy.
Subject(s)
Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/economics , Pneumococcal Vaccines/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Germany/epidemiology , Health Care Costs , Heptavalent Pneumococcal Conjugate Vaccine , Humans , Infant , Infant, Newborn , Male , Middle Aged , Models, Statistical , North America/epidemiology , Norway/epidemiology , Pneumococcal Infections/economics , Pneumococcal Vaccines/administration & dosage , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Previous studies have shown that interleukin-8 serum levels in febrile neutropenic patients are significantly higher in patients with gram-negative bacteremia than in patients with other causes of fever and may indicate unfavorable outcomes. We assessed the value of interleukin-8 serum levels at fever onset to predict clinical complications in order to confirm these earlier findings. PATIENTS AND METHODS: In a prospective observational study of adult patients receiving cancer chemotherapy, serum samples obtained at the onset of 147 febrile neutropenic episodes were measured by an immunoluminescence assay. RESULTS: Complicated courses of fever including severe sepsis or septic shock, respiratory insufficiency or death were observed in 13 episodes (9%); in six episodes complications had developed within 1 week after fever onset and five of them were associated with bloodstream infections. At an interleukin-8 cutoff level of 1,000 pg/ml, these early complications were predicted with a sensitivity of 83%, a specificity of 97%, a positive predictive value of 50%, and a negative predictive value of 99%, respectively. CONCLUSION: Interleukin-8 levels at fever onset may be used for the prediction of early medical complications associated with bacteremia and can help identify patients who might benefit from intensive care admission.