Outcomes of chronic myeloid leukemia patients after therapeutic failure to conventional tyrosine kinase inhibitors and asciminib.

Patients with chronic myeloid leukemia (CML) who have failed conventional tyrosine kinase inhibitors (cTKIs) and asciminib constitute a complex group of patients with few therapeutic options. A retrospective descriptive multicenter observational study was carried out including patients with CML who had presented a therapeutic failure to ≥ 2 cTKIs and asciminib, and had received or were not candidates to ponatinib. Of the 19 patients enrolled, 8 patients failed asciminib due to intolerance and 11 due to resistance. The most common strategy for intolerant patients was to initiate a previously administered cTKI (6/8) with dose adjustments or symptomatic management of adverse events (AEs). Of the patients who failed due to resistance, only patients who underwent progenitor transplantation achieved profound long-term responses. A frequent strategy was to use ponatinib (4/11) in patients previously considered non-candidates, with poor responses in patients in whom dose reductions were used, and severe AEs in patients at standard doses. In the remaining patients, cTKIs and other agents (interferon, hydroxyurea, citarabine, busulfan) were used with poor responses. Patients who progressed to advanced stages had a dismal prognosis. With a median follow-up of 11.2 months, overall survival of the global cohort was 73%; 100% for intolerant patients, 71% for resistant patients and 25% for those who discontinue asciminib in accelerated/blastic phase.

Comparing clinical trial population representativeness to real-world users of 17 biologics approved for immune-mediated inflammatory diseases: An external validity analysis of 66,639 biologic users from the Italian VALORE project.

To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients' characteristics and median treatment duration of biologics approved for IMIDs between RCTs' and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8-1.9) compared to RCTs (F/M ratio: 0.5-0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4-100 vs. 6-167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients.

Outcomes of polatuzumab vedotin-containing regimens in real-world setting of relapsed and or refractory diffuse large B-cell lymphoma patients: a matched-control analysis from the Thai Lymphoma Study Group (TLSG).

Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) is a challenging condition to treat, and there is an unmet clinical need for effective therapies. Recently, polatuzumab vedotin (Pola), an anti-CD79b antibody-drug-conjugate (ADC), combined with bendamustine-rituximab (BR), has been approved for R/R DLBCL patients. However, real-world data on Pola-based regimens in R/R DLBCL patients, especially in Thailand, are limited. This study aimed to evaluate the efficacy and safety of Pola-based salvage treatment in R/R DLBCL patients in Thailand. Thirty-five patients who received Pola-based treatment were included in the study, and their data were compared to 180 matched patients who received non-Pola-based therapy. The overall response rate (ORR) in the Pola group was 62.8%, with complete remission and partial remission rates of 17.1% and 45.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 10.6 months and 12.8 months, respectively. The study found a significantly higher ORR in Pola-based salvage treatments compared to non-Pola-based therapy (62.8% vs. 33.3%). The survival outcomes were also significantly superior in the Pola group, with longer median PFS and OS than the control group. Grades 3-4 adverse events (AEs) were mainly hematological, and they were tolerable. In conclusion, this study provides real-world evidence of the efficacy and safety of Pola-based salvage treatment in R/R DLBCL patients in Thailand. The results of this study are promising and suggest that Pola-based salvage treatment could be a viable option for R/R DLBCL patients who have limited treatment options.

Delayed pregnancy detection and return to fertility with extended levonorgestrel-containing oral contraceptives: A real world setting cohort study.

PURPOSE: As part of the European risk management plan of a 91-day extended levonorgestrel-containing combined oral contraceptive (COCLNG ), a study was performed to assess its safety. This analysis was conducted to examine delayed pregnancy detection and return to fertility with extended combined oral contraceptives (COC). METHODS: We conducted a retrospective cohort study in new users of 91-day COCLNG or 28-day COCLNG within a US-based healthcare claims database from 2006 to 2017. Delayed pregnancy detection during current COCLNG exposure was defined as the time between estimated pregnancy start and first prenatal care encounter. Additionally, the time between estimated pregnancy start and COCLNG discontinuation was measured. To measure return to fertility, pregnancy rates were estimated among females who discontinued treatment. 91-day COCLNG users were propensity score-matched to 28-day COCLNG users. Hazard ratio for pregnancy was calculated using Cox proportional hazards models. RESULTS: The 91-day and 28-day COCLNG users had 25 593 and 76 586 treatment episodes, respectively. The median time to pregnancy detection was 64.5 and 61.0 days (p = 0.24) in users of 91-day COCLNG and 28-day COCLNG . The median exposure time to treatment after estimated pregnancy start was 54.0 and 38.0 days (p < 0.01). In the fertility analysis, pregnancy rates were 54.82 (95% CI, 50.05-59.93) and 69.30 (95% CI, 64.98-73.82) per 1000 person-years in extended COCLNG discontinuers and 28-day COCLNG discontinuers. The adjusted hazard ratio of pregnancy was 0.77 (95% CI, 0.69-0.85). CONCLUSIONS: Small differences were observed for pregnancy rates and delayed pregnancy detection between 91-day extended COCLNG and 28-day COCLNG , which may be related to the longer days' supply of extended COCLNG . Differences in the fertility analysis may be related to unmeasured residual confounding.

Re-evaluation of modifiable risk factors for obstetric anal sphincter injury in a real-world setting.

INTRODUCTION AND HYPOTHESIS: The objective was to identify modifiable risk factors for obstetric anal sphincter injury (OASI) in primiparous women. METHODS: This was a retrospective cohort study of primiparous women with a singleton vaginal delivery. Main outcome measures were incidence of OASI and odds ratios for possible risk factors: maternal age, body mass index and height, fetal birthweight and head circumference, gestational age, epidural analgesia, mediolateral episiotomy, and instrumental deliveries. Univariate and multivariate logistic regressions were performed using forward methods for variable selection. RESULTS: Of 19,786 primiparous women with a singleton vaginal delivery, 369 sustained an OASI (1.9%). Risk factors were identified: vacuum extraction (adjusted OR 2.06, 95% CI, 1.59-2.65, p < 0.001), increased fetal weight (aOR 1.06, 95% CI, 1.02-1.11, p = 0.002, per 100-g increments); head circumference (aOR 1.24, 95% CI, 1.13-1.35, p < 0.001, per 1-cm increments); gestational week (aOR 1.11, 95% CI, 1.02-1.2, p = 0.012, per week). Protective factors: mediolateral episiotomy (aOR 0.75, 95% CI, 0.59-0.94, p = 0.013) particularly in vacuum deliveries (aOR 0.50, 95% CI, 0.29-0.97, p = 0.040); epidural analgesia (aOR 0.64, 95% CI, 0.48-0.84, p = 0.001); maternal height ≥157 cm (aOR 0.97, 95% CI, 0.96-0.98, p = 0.006, risk decreases by 2.6% per 1 cm increase in height). CONCLUSIONS: Mediolateral episiotomy was protective against OASI in both spontaneous and instrumental deliveries of primiparae. Increased fetal weight and large fetal head circumference, particularly in short women, were significant risk factors. These findings support the performance of ultrasound to acquire updated fetal measures before admission to the labor ward.

Implementing medication adherence interventions in four Dutch living labs; context matters.

BACKGROUND: Despite the abundant availability of effective medication adherence interventions, uptake of these interventions into routine care often lacks. Examples of effective medication adherence interventions include telephone counseling, consult preparation and the teach-back method. Assessing context is an important step in understanding implementation success of interventions, but context is often not reported or only moderately described. This study aims to describe context-specific characteristics in four living labs prior to the implementation of evidence-based interventions aiming to improve medication adherence. METHODS: A qualitative study was conducted within four living labs using individual interviews (n = 12) and focus groups (n = 4) with project leaders and involved healthcare providers. The four living labs are multidisciplinary collaboratives that are early adopters of medication adherence interventions in the Dutch primary care system. Context is defined as the environment or setting in which the proposed change is to be implemented. Interview topics to assess context were formulated based on the 'inner setting' and 'outer setting' domains of the Consolidated Framework for Implementation Research (CFIR). Interviews were recorded and transcribed verbatim. Transcripts were deductively analyzed. RESULTS: A total of 39 community pharmacists, pharmacy technicians, general practitioners and a home care employee participated in the (focus group) interviews. All four living labs proved to be pharmacy-driven and characterized by a high regard for innovation by staff members, a positive implementation climate, high levels of leadership engagement and high compatibility between the living labs and the interventions. Two living labs were larger in size and characterized by more formal communication. Two living labs were characterized by higher levels of cosmopolitanism which resulted in more adaptable interventions. Worries about external policy, most notably lack of reimbursement for sustainment and upscaling of the interventions, were shared among all living labs. CONCLUSIONS: Contextual characteristics of four living labs that are early adopters of medication adherence interventions provide detailed examples of a positive implementation setting. These can be used to inform dissemination of medication adherence interventions in settings less experienced in implementing medication adherence interventions.

Effectiveness of enhanced cognitive behaviour therapy for patients aged 14 to 25: A promising treatment for anorexia nervosa in transition-age youth.

OBJECTIVE: The study aimed to evaluate the effectiveness of enhanced cognitive behaviour therapy (CBT-E) on patients with anorexia nervosa (AN) aged 14 to 25 treated in a real-world setting. METHOD: One hundred and fifteen patients with AN (n = 61, age <18 years) were recruited from consecutive referrals to a clinical eating disorder service offering outpatient CBT-E. Body Mass Index (BMI), BMI centiles, Eating Disorder Examination Questionnaire, Brief Symptom Inventory, and Clinical Impairment Assessment scores were recorded at admission, at the end of treatment, and at 20-week follow-up. RESULTS: The seventy-two patients (62.6%) who finished the programme showed considerable weight gain and reduced scores for clinical impairment and eating-disorder and general psychopathology. Changes remained stable at 20 weeks. A comparison between adolescent and adult patients indicates similar improvements in eating-disorder psychopathology. CONCLUSIONS: The benchmark data yielded by this study suggest that CBT-E is a well-accepted and promising treatment that could be adopted to ensure continuity of care across the transitional age.

Treatment-Free Remission in Real-World Chronic Myeloid Leukemia Patients: Insights from German Hematology Practices.

INTRODUCTION: Treatment-free remission (TFR) is increasingly considered as treatment goal for patients with chronic myeloid leukemia (CML), but information on the disposition and outcome of TFR in clinical practice is scarce. Here, we report the characteristics of patients with CML in deep molecular remission (DMR) and/or after an attempt of TFR reported by 33 German hematologists. METHODS: Data were collected retrospectively by means of a questionnaire. Patients were eligible if they had either discontinued tyrosine kinase inhibitor (TKI) therapy or had achieved DMR of at least MR4 (BCR-ABL ≤0.01%) prior to the time-point of data collection. RESULTS: 797 patients were included in the analysis, out of which 281 patients had been discontinued from TKI treatment. TKI discontinuation rates among practices were variable, ranging from 0 to 36 patients. Mean time from TKI initiation to discontinuation was 7.2 years; mean duration of MR4 before TFR was 3.5 years. At the time of entering TFR, most patients (90.8%) had achieved a deep molecular response (≥MR4). BCR-ABL monitoring during TFR was performed heterogeneously: Within the first 6 months of TFR, 58.6% of the practices reported mean monitoring intervals of <6 weeks, while 20.7% employed intervals >8 weeks. After entering TFR, 53.2% of patients remained in MR4 or better. TKI treatment was reinitiated in 108 patients, mainly for loss of major molecular remission. CONCLUSIONS: These clinical data from a German real-life population show that TKI discontinuation is feasible in clinical practice. Outcomes appear to be comparable to those reported in clinical trials, but molecular monitoring in TFR is rather variable.

Adverse drug reaction reporting quality among different health professionals and the contribution of clinical pharmacists: A pilot study.

WHAT IS KNOWN AND OBJECTIVE: Adverse drug reaction (ADR) reporting is generally of poor quality, which may delay post-marketing regulatory actions. Here, we evaluated the quality of ADR reporting at our institution and examined the roles of clinical pharmacists in this process. METHODS: We retrospectively reviewed ADR reports at our hospital between 2017 and 2019 to assess the number, source, drugs, and routes of administration. The quality assessment of ADR case reports form issued by the China Adverse Drug Reaction Monitoring Centre was used to assess the quality of ADR reports. Quality scores of ADR reports from pharmacists and nonpharmacists were assessed before and after review by clinical pharmacists. RESULTS AND DISCUSSION: Reports of adverse drug reaction reporting by healthcare professionals increased annually, with 59, 77 and 82 reports submitted in 2017, 2018 and 2019, respectively. The numbers of new or serious ADR reports by healthcare professionals in 2017, 2018, and 2019 were 5 (8.47%), 77 (11.69%) and 82 (10.98%), respectively. New or serious ADR reports accounted for approximately 10% (23/218) of all reported cases, and more than 70% (158/218) of the reports were from pharmacists. Systemic administration accounted for more than 80% (233/265) of adverse reactions, whereas ADRs due to topical drug use were rarely reported. The drugs that reportedly triggered ADRs were mainly antibacterial and patented Chinese medicines and accounted for more than half of all reported cases. The scores of ADR reports from pharmacists and nonpharmacists before modification by clinical pharmacists were 86.69 ± 8.12 and 68.36 ± 5.94, respectively, and the scores of ADR reports from pharmacists and nonpharmacists after modification by clinical pharmacists were 91.14 ± 6.64 and 90.02 ± 5.63, respectively. WHAT IS NEW AND CONCLUSION: In a real-world setting, pharmacists are commonly responsible for most ADR reports. The quality of ADR reports from pharmacists and nonpharmacists before review did not reach the standard of excellence. An audit of clinical pharmacists may improve the overall quality of ADR reports. However, under-reporting of adverse reactions still occurs.

Molecular-targeted Therapy for Metastatic Renal Cell Carcinoma As First-line Therapy: A Single Institution 13-year Experience.

We aimed to identify the role of first-line monotherapy with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in patients with metastatic RCC. Eligible patients were categorized into three groups (favorable, intermediate, and poor risk) according to the International Metastatic RCC Database Consortium risk criteria. Overall survival (OS) was the primary endpoint. Survival was compared using the log-rank test. A total of 108 patients were retrospectively analyzed. The numbers of patients in the favorable-, intermediate-, and poor-risk groups were 32 (30%), 66 (61%), and 10 (9%), repestively. The median OS values in the entire cohort was 36 months (95% confidence interval [CI] 29-53). The median OS in the favorable, intermediate, and poor risk groups were 94 months (95% CI: 43-Not reached), 30 months (95% CI: 20-38), and 8 months (95% CI: 0-Not reached), respectively (p<0.05). Prior nephrectomy, clear cell histology, clinical T stage ≤2, no metastasis at the time of diagnosis, nivolumab beyond first-line therapy, and objective response to VEGFR-TKIs were factors significantly prolonging OS on univariate analysis. VEGFR-TKI monotherapy as first-line therapy was an effective treatment option for patients with metastatic clear cell RCC with favorable risk.

Safety and complications of catheter ablation for atrial fibrillation: Predictors of complications from an updated analysis the National Inpatient Database.

BACKGROUND: Catheter ablation is increasingly employed in the management of atrial fibrillation (AF). Data regarding safety of ablation of AF is largely derived from controlled clinical trials. OBJECTIVES: The aim of this study was to analyze safety and complications of AF ablation performed in a "real world" setting outside of clinical trials, and obtain insights on predictors of complications. METHODS: We utilized the National Inpatient Sample database, to identify all patients who underwent AF ablations between 2015 and 2017 using International Classification of Disease-Tenth revision codes. Complications were defined as per the Agency for Health Care Research and Quality Guidelines. Statistical tests including multivariate logistic regression were performed to determine predictors of complications. RESULTS: Among 14,875 cases of AF ablation between 2015 and 2017, a total of 1884 complications were identified among 1080 (7.2%) patients. Patients with complications were likely to be older and female with a higher burden of comorbidities. A 27% increase in complications was observed from 2015 to 2017, driven by an increase in pericardial complications. Multivariate regression analysis revealed that pulmonary hypertension (adjusted odds ratio [aOR]: 1.99, p = .041) and chronic kidney disease (CKD; aOR: 1.67, p = .024), were independent predictors of complications. Centers with higher procedural volumes were associated with lower complication rates. CONCLUSIONS: Complication rates related to AF ablations remain substantially high. Presence of pulmonary hypertension and CKD are predictive of higher procedural complications. Furthermore, hospital procedure volume is an important factor that correlates with complication rates.

Perampanel treatment in highly drug-resistant epilepsies including nonsurgical candidates and failed surgery.

OBJECTIVE: To evaluate the effectiveness and tolerability of perampanel (PER) treatment for patients with highly drug-resistant epilepsies (HDRE) including nonsurgical candidates and failed surgery in real-world setting. METHODS: All patients who were treated with PER during June 2015 to August 2019 were selected. Primary outcomes were percentage of seizure reduction, responder rate, and seizure freedom rate. Seizure frequency after taking PER at 3 and 12 months were compared with baseline seizure frequency within the same time period prior to starting PER. Secondary outcomes were retention rate, side effects, and predictors for a response to PER. Descriptive statistics and the Kernel regression model were employed. RESULTS: Forty-one patients received PER treatment during the study period. Six patients who had no baseline seizure frequency recordings were excluded, for a total of 35 patients included for analysis. Mean age was 40.06 years (SD 12.34). All were highly resistant to several antiseizure drugs (ASDs) with a median number of previously failed ASDs of 8 items. Eleven, 16, 5, and 3 patients were lesional, nonlesional focal epilepsy, nonsurgical candidate, and failed surgery, respectively. At 3 months after PER treatment, the median percentage of seizure reduction was 20 % (-35.71, 100), the responder rate was 22.86 % (8/35), and the seizure freedom rate was 17.14% (6/35). At 12 months after PER treatment, the corresponding outcomes were 25% (-20.57, 91.60), 22.58% (7/31), and 9.68% (3/31), respectively. Retention rates at 3 and 12 months were 100% and 91.43% (32/35), respectively. Nineteen patients (54.29%) experienced side effects from PER. Side effects were somnolence (6/35), dizziness (3/35), irritability (2/35), and ataxia (2/35), and one each for weight loss, nausea, headache, insomnia, verbal aggressivity, and depression. Median duration for 2-mg dose increment was 2.2 months. CONCLUSIONS: In real-world practice, slow-titration PER regimen is well-tolerable and shows benefit in helping control seizures in patients with very difficult-to-treat HDRE.

Asthma in the Real-World: The Relevance of Gender.

BACKGROUND: The possible gender impact on asthma arouses current and outstanding interest, but few studies addressed this issue in the real-world setting. OBJECTIVE: This cross-sectional study tested the hypothesis of a potential difference between asthmatic males and females in a real-life setting, such as a third-level asthma clinic. METHODS: A total of 499 asthmatic outpatients (301 females and 198 males, mean age 58.25 years) were consecutively visited. The visit included history, asthma control, and severity grade, physical examination, lung function, fractional exhaled nitric oxide assessment, and blood sample for biomarkers. RESULTS: There were more females than males (about 3 of 5). Asthmatic females smoked less (p < 0.0001) than males and had higher FEV1 (p = 0.0022) and FVC (p = 0.0004) values than asthmatic males. CONCLUSIONS: Gender difference was associated with smoking and lung function impairment; thus, this issue should be carefully considered in asthmatic patients in daily clinical practice.

Vagus nerve stimulation as adjunctive therapy in patients with difficult-to-treat depression (RESTORE-LIFE): study protocol design and rationale of a real-world post-market study.

BACKGROUND: Depressive illness is associated with significant adverse consequences for patients and their families, and for society. Clinical challenges are encountered in the management of patients suffering from depression whether they are designated difficult-to-treat or treatment-resistant. Prospective serial depression treatment trials have shown that less than 40% of patients with major depressive disorder remit with an initial pharmacotherapy trial, and a progressively smaller proportion of patients remit with each subsequent trial. For patients who suffer from difficult-to-treat depression (DTD), treatments should focus on patient-centred symptom control, patient functioning, and improving patient quality of life. Among the treatment options for patients with DTD is Vagus Nerve Stimulation (VNS) Therapy. VNS Therapy involves intermittent electrical stimulation of the left cervical vagus nerve and has been shown to be efficacious for long-term management of patients with DTD. METHODS: RESTORE-LIFE is a prospective, observational, multi-site, global post-market study intended to assess short-, mid-, and long-term effectiveness and efficiency outcomes in a 'real-world' setting among patients with DTD treated with adjunctive VNS Therapy. A minimum of 500 patients will be implanted with a VNS Therapy System at up to 80 global sites. Eligible patients will participate in a baseline visit between 1 and 6 weeks before device implant and will be followed for a minimum of 36 months and a maximum of 60 months. The diagnosis of depression and comorbid disorders will be determined using the Mini-International Neuropsychiatric Interview (MINI). The primary endpoint is response rate, defined as a decrease of ≥50% in Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to 12 months post-implant. DISCUSSION: A standardized approach in the management of DTD may not be appropriate for the treatment of such a complex heterogenous patient population. This study has been designed to evaluate whether VNS Therapy meaningfully improves and sustains clinical and depressive symptom outcomes in patients with DTD. This study will investigate the durability of VNS response in DTD and utility of VNS for long-term disease management of DTD. In addition, the study results will potentially clarify clinical, functional, and health economic questions in a real-world patient population with DTD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03320304. Registered 25 October 2017.

Differential response to intravitreal dexamethasone implant in naïve and previously treated diabetic macular edema eyes.

BACKGROUND: To identify different response patterns to intravitreal dexamethasone implants (IDI) in naïve and previously treated (PT) diabetic macular edema (DME) eyes in a real-life setting. METHODS: 342 IDI injections (203 DME eyes) were included. Number of IDI injections, percentage (%) of eyes with 1, 2, 3 and ≥ 4 injections, time to reinjections, visual acuity (VA), intraocular pressure (IOP) and central retinal thickness (CRT) were evaluated for naïve and PT DME eyes over 24 months. RESULTS: Mean number of injections was significantly lower in naïve vs PT DME eyes (1.40 ± 0.9 vs 1.82 ± 0.9, p < 0.001). The percentage of eyes receiving 1 injection was significantly higher in naïve vs PT DME eyes (76.1 vs 47.7), (p < 0.001). However, it was significantly lower for 2 (16.4 vs 29.4), or 3 injections (1.4 vs 17.6) (both p < 0.001), with no differences in eyes receiving ≥4 injections (5.9 vs 5.1 respectively, p = 0.80). Mean time to reinjection was not significantly different between both groups for the second, third and fourth injection (9.6 ± 4.0 vs 10.0 ± 5.5, p = 0.75, 13.2 ± 4.0 vs 16.0 ± 3.5, p = 0.21 and 21.7 ± 3.8 vs 19.7 ± 5.8, p = 0.55). VA scores were consistently better in naïve vs PT DME eyes at all studied timepoints, with no significant differences in CRT reduction or adverse effect rates. CONCLUSION: Naïve DME eyes received lower number of IDI injections and showed better VA levels than PT DME eyes for 24 months in a real-world setting. This data supports the IDI use in early DME stages and provide further evidence of better IDI response when used as first-line therapy.

Impact and implementation of Healthy Life Centres, a primary-care service intervention for behaviour change in Norway: Study design.

Aims: This ongoing study is investigating the implementation and long-term impact of Healthy Life Centres (HLCs), a primary-care service intervention for behaviour change in Norway. The primary aim is to study changes in objectively measured physical activity (PA) levels following a HLC intervention in the short (three months) and long term (15 months). Furthermore, the study is evaluating determinants concerning implementation and adaption of the HLC intervention that influence reach and impact on participants outcomes. Methods: This prospective observational study includes 32 HLCs from four different geographical regions in Norway. Subjects aged ⩾18 years were invited to participate. The study has a pre-post design with a 15-month follow-up. The HLC intervention is a three-month individualised program, containing personal consultations and group-based behaviour-specific courses on PA, diet and smoking cessation. Data collection consists of registration of objectively measured PA level, physical examinations, interviews and questionnaires. In addition, HLC organisation, offers, professions and resources are being examined. The Reach, Efficacy/Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework is being applied to study the external validation of the HLC intervention. The study enrolled 1020 participants who gave their written informed consent. Post-tests and follow-up data collection is still ongoing and will continue until August 2019. Conclusions: By exploring the HLC intervention in a real-world setting and addressing the elements of RE-AIM, this study will contribute to an improved understanding and development of effective primary-care behaviour interventions such as the HLC model. The strengths of the study are the large sample size and the many HLCs and regions included.

Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience.

Data from 423 human epidermal growth factor receptor 2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6-35.4) and clinical benefit was 52.7% (95% CI, 48-57.5). ORR was negatively affected by prior exposure to everolimus/exemestane ( p = 0.002) and favorably influenced by early line-treatment ( p < 0.0001). At 6 months, median progression-free survival was 12 months (95% CI, 8-16) and median overall survival was 24 months (95% CI, 17-30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2-, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained.

Use of subcutaneous and intravenous trastuzumab: real-world experience from three hospitals in Sweden.

Aim: We aimed to describe the use of subcutaneous (sc.) trastuzumab use in a real-world setting. Patients & methods: This retrospective cohort study evaluated electronic medical records of patients with early breast cancer and trastuzumab use from January 2010 to February 2018 in three hospitals in Sweden. Results: In total, 363 patients received trastuzumab during study period. Of these, 217 (59.8%) patients started treatment with sc. trastuzumab and 146 (40.2%) with intravenous trastuzumab. After sc. trastuzumab approval, use of sc. trastuzumab increased from 70.2% in 2014 to 100% in 2017. Since 2013, 34 of 35 (97.4%) patients who started with intravenous trastuzumab switched to sc. formulation. Conclusion: Trastuzumab sc. quickly became the prevailing formulation for treatment in HER2-positive early breast cancer.

Safety and efficacy of cabazitaxel in 660 patients with metastatic castration-resistant prostate cancer in real-world settings: results of a Japanese post-marketing surveillance study.

OBJECTIVE: To evaluate the real-world safety and efficacy of cabazitaxel in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel-containing regimen. METHODS: This prospective multicenter observational study registered all patients with mCRPC treated with cabazitaxel following its launch in Japan in September 2014. Patient enrollment continued until at least 500 patients were enrolled. Adverse drug reactions (ADRs) were evaluated according to CTCAE ver. 4.0. Efficacy endpoints were assessed for up to 1 year, and included prostate specific antigen (PSA) response rates (defined as a decrease of ≥30% or ≥50% from baseline), overall survival (OS), and time to treatment failure (TTF). RESULTS: A total of 660 mCRPC patients were enrolled across 316 centers by June 2016. Frequent ADRs (any grade) were neutropenia (49.1%), febrile neutropenia (18.0%) and anemia (15.0%). Most ADRs occurred in cycle 1. Neutropenia and febrile neutropenia were significantly less frequent in patients who received prophylactic granulocyte colony-stimulating factor. The PSA response rates for decrease of ≥30% or ≥50% from baseline were 28.1% and 17.5%, respectively, in patients with baseline PSA of ≥5 ng/ml. Median OS and TTF were 319 days (95% confidence interval: 293.0-361.0) and 116 days (95% confidence interval: 108.0-135.0), respectively. CONCLUSIONS: This study of cabazitaxel in 660 Japanese patients treated in real-world settings, the largest study of cabazitaxel to date, demonstrated a safety profile that was generally consistent with those of pivotal clinical studies. Cabazitaxel was also effective in terms of the PSA response, OS, and TTF.