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.

Is it acceptable to destroy or include human embryos before day 5 in research programmes?

Day-3 poor-quality embryos (PQE) from IVF-embryo transfer cycles are usually destroyed or are included in research programmes. Knowing that these embryos have the ability to evolve to the blastocyst stage and yield embryonic stem cell lines, this study postulated that they could also give rise to live births. This is a prospective study including 186 IVF-embryo transfer candidates who had obtained at least one supernumerary PQE on day 3. PQE were kept for extended culture and high-quality blastocysts were frozen. A total of 620 PQE were eligible for the study, 217 (35.0%) reached the blastocyst stage and 73 (33.6%) were frozen. Blastulation rates were 7-fold higher (OR 7.29, 95% CI 5.01-10.61) in embryos compacted on day 4. Of the frozen blastocysts, 40 were thawed during 33 thawed blastocyst transfer cycles, which led to 10 clinical pregnancies. These pregnancies resulted in five miscarriages and five healthy live births at full term. PQE may achieve their development to the blastocyst stage, be frozen-thawed and harbour reasonable implantation potential. These results, thereby, raise an ethical issue regarding the fate reserved to PQE.

Antidepressant treatment patterns in younger and older adults from the general population in a real-life setting.

OBJECTIVE: The treatment of depression in real-life settings appears to be influenced by health care systems. Antidepressant drugs have been found to be underused in the older population relative to younger adults when refunding of such drugs is poor. No study assessed the pattern of antidepressant use according to age in a universal health care system. The objective is to assess whether the pattern of antidepressant drug use differs between younger and older adults with respect to treatment duration, adherence to treatment, coprescription of other psychotropic drugs, switch, or combination of antidepressant drugs. METHODS: A historical cohort study included 7747 older (65+ years) and 27,306 younger (younger than 65 years) adults representative of the beneficiaries of the French national health care insurance system who initiated a new antidepressant treatment. Follow-up after treatment initiation was at least 6 months. RESULTS: Older patients had a significantly longer duration of treatment than younger adults (hazard ratio = 0.90; 95%CI[0.88-0.93]). Adherence was more often good in older than in younger adults when the treatment was initiated by a general practitioner (23.4% vs. 16.7%; Odds ratio (OR) = 1.35[1.25-1.46]), a hospital practitioner (OR = 1.68[1.40-2.03]) or another specialist (OR = 1.60[1.19-2.17]). The coprescription of psychotropic drugs decreased with older age in men (OR = 0.77[0.70-0.85]) and increased with older age in women (OR = 1.14[1.07-1.22]). Switches and combinations of antidepressants were not associated with age. CONCLUSION: In a universal health care system, with similar reimbursement of drugs regardless of age, treatment duration, and adherence were better in the older patients than in the younger ones.

Trastuzumab emtansine vs lapatinib and capecitabine in HER2-positive metastatic breast cancer brain metastases: A real-world study.

BACKGROUND: Trastuzumab emtansine (T-DM1) has demonstrated improvements in survival and neurological symptoms in patients with breast cancer with brain metastases (BCBM). This real-world study investigated the effectiveness of T-DM1 versus lapatinib plus capecitabine (LC) in patients with BCBM. METHODS: This retrospective, observational study evaluated patients with HER2-positive BCBM using a real-world database. Eligible patients had initiated T-DM1 or LC with a prior diagnosis of brain metastasis and ≥1 prior metastatic breast cancer treatment. The primary endpoint was overall survival (OS); secondary endpoints were time to next relevant treatment or death (TTNT) and real-world progression-free survival (rwPFS). An inverse probability of treatment weighting (IPTW) approach was used to account for differences in potential baseline characteristics between treatment groups. Outcomes were described using the Kaplan-Meier method, and the average treatment effect of initiating T-DM1 versus LC was estimated using weighted Cox proportional hazard models and hazard ratio (HR). RESULTS: A total of 214 patients were available for analysis (T-DM1, n = 161; LC, n = 53). Demographics and baseline characteristics were generally well-balanced between treatment groups after weighting. After weighting, median OS was 17.7 (T-DM1) versus 9.6 (LC) months (HR, 0.55 [95% CI, 0.34-0.89]; P=0.013). Median TTNT was 9.0 (T-DM1) versus 6.0 (LC) months (HR, 0.55 [95% CI, 0.36-0.85]; P = 0.005). After weighting, median rwPFS was 6.0 (T-DM1) versus 4.0 (LC) months (HR, 0.50 [95% CI, 0.36-0.69]; P < 0.001). CONCLUSIONS: These results support the superior effectiveness and clinical relevance of T-DM1 versus LC in patients with HER2-positive BCBM in the real world.

Real-World First-Line Use of Pertuzumab With Different Taxanes for Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: A Comparative Effectiveness Study Using US Electronic Health Records.

PURPOSE: On the basis of the results from CLEOPATRA, pertuzumab plus trastuzumab and chemotherapy is the first-line standard of care for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, discrepancies have been reported between clinical trial and real-world outcomes. We report real-world outcomes for patients with HER2-positive MBC treated with first-line pertuzumab plus trastuzumab and a taxane in routine clinical practice in the United States. METHODS: A retrospective analysis was conducted using electronic health record-derived deidentified data from the Flatiron Health database. Patients were grouped according to the first taxane received (paclitaxel/nab-paclitaxel or docetaxel). Median real-world progression-free survival (rwPFS) and overall survival (rwOS) was estimated using Kaplan-Meier methodology. Subgroup analyses were conducted in patients treated with docetaxel who met CLEOPATRA's key eligibility criteria. RESULTS: We included 1,065 patients; 313 patients received paclitaxel/nab-paclitaxel and 752 received docetaxel. Patients who received paclitaxel/nab-paclitaxel were older, had a worse Eastern Cooperative Oncology Group Performance Status, and had more recurrent metastatic disease compared with the docetaxel group. After adjustment for potential confounders, similar median rwPFS (inverse probability of treatment weighted average treatment effect for the treated [IPTW-ATT] hazard ratio [HR], 1.09; 95% CI, 0.9 to 1.3; P = .365) and rwOS (IPTW-ATT HR, 1.23; 95% CI, 0.96 to 1.58; P = .101) was observed between treatment groups. In the subgroup of CLEOPATRA-eligible patients, median rwPFS and rwOS were 16.9 months and 57.8 months, respectively. CONCLUSION: There was no statistically significant difference in real-world outcomes between patients treated with paclitaxel/nab-paclitaxel and those treated with docetaxel. Selecting patients using key CLEOPATRA eligibility criteria resulted in rwPFS and rwOS similar to those observed in CLEOPATRA, highlighting the importance of ensuring similar patient populations when comparing clinical trial and real-world data.

Von Willebrand factor and ADAMTS13: a candidate couple for preeclampsia pathophysiology.

OBJECTIVE: The goal of this study was to search for an association between a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) levels and the occurrence of preeclampsia, its characteristics (time-onset and severity), and its consequences (occurrence of fetal growth restriction or preterm delivery). METHODS AND RESULTS: We studied 140 pairs of women in a case-control study with 3 matching criteria: maternal age, gestational age, and ethnic origin. We measured ADAMTS13 activity using a fluorescence resonance energy transfer assay with the fluorescence resonance energy transfer-VWF73 peptide. ELISA was used to assess protein antigen levels: ADAMTS13, von Willebrand Factor (VWF), interleukin-6, C-reactive protein, P-selectin, and thrombospondin-1. The lowest levels of ADAMTS13 (activity ≤ 70% or antigen ≤ 592 ng/mL) were significantly associated with preeclampsia (odds ratios [OR] [95% confidence interval] of 4.2 [1.1 to 15] and 14.3 [1.7 to 123], respectively). This association was independent of VWF levels and preeclampsia risk factors but dependent on interleukin-6 and C-reactive protein levels for ADAMTS13 activity. Levels of ADAMTS13 activity (≤ 57%) were significantly associated with early-onset preeclampsia (OR = 2.5 [1.1 to 5.8]). Severe preeclampsia was associated with the highest levels of P-selectin (>57 ng/mL) (OR = 3.4 [1.2 to 9.7]). CONCLUSIONS: Preeclampsia is associated with decreased levels of ADAMTS13, independently of VWF. This decrease is quantitative, occurs early, and seems to be dependent on inflammation. Our results suggest that ADAMTS13 could participate in the pathophysiology of preeclampsia.

Trastuzumab-based regimens beyond progression: A crucial treatment option for HER2+ advanced/metastatic breast cancer.

Upon its establishment for the treatment of metastatic breast cancer (mBC), continuing trastuzumab beyond disease progression was an important paradigm shift that became the recommendation by major guidelines. However, data supporting continuation of human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab beyond the second-line setting are limited, resulting in a lack of approval of, or access to, this therapeutic strategy in many countries. This study aimed to provide additional data on the continued use of trastuzumab and trastuzumab-based therapies in combination with chemotherapy (CT) as third-line treatment for patients with mBC. This open-cohort, retrospective, observational study used deidentified patient-level data from an electronic health record-derived database that included patients with mBC who initiated third-line treatment with trastuzumab-based therapy combined with CT (Tras + CT; n = 288) or CT alone (CT; n = 49). Patients who received Tras + CT had a longer weighted median overall survival vs those who received CT only: 20.6 months (95% CI, 18.3-26.4 months) vs 10.1 months (95% CI, 7.8-12.3 months), respectively (hazard ratio [HR], 0.29; 95% CI, 0.16-0.53). This study provides additional support for maintaining trastuzumab-based therapies for patients with HER2+ mBC beyond second-line treatment. This treatment option should be available for all patients with mBC worldwide.

T-DM1 after Pertuzumab plus Trastuzumab: Treatment Sequence-Induced Selection Bias in HER2-Positive Metastatic Breast Cancer.

Real-world studies have suggested decreased trastuzumab emtansine (T-DM1) effectiveness in patients with metastatic breast cancer (mBC) who received prior trastuzumab plus pertuzumab (H + P). However, these studies may have been biased toward pertuzumab-experienced patients with more aggressive disease. Using an electronic health record-derived database, patients diagnosed with mBC on/after 1 January 2011 who initiated T-DM1 in any treatment line (primary cohort) or who initiated second-line T-DM1 following first-line H ± P (secondary cohort) from 22 February 2013 to 31 December 2019 were included. The primary outcome was time from index date to next treatment or death (TTNT). In the primary cohort (n = 757), the percentage of patients with prior P increased from 37% to 73% across the study period, while population characteristics and treatment effectiveness measures were generally stable. Among P-experienced patients from the secondary cohort (n = 246), median time from mBC diagnosis to T-DM1 initiation increased from 10 to 14 months (2013-2019), and median TTNT increased from 4.4 to 10.2 months (2013-2018). Over time, prior H + P prevalence significantly increased with no observable impact on T-DM1 effectiveness. Drug approval timing should be considered when assessing treatment effectiveness within a sequence.

Depressed older adults may be less cared for than depressed younger ones.

The aim of the study was to investigate depression treatment use, either psychotherapy (PT) or antidepressant drugs (ADT) in the older and younger depressed population. Cohorts of 6316 elderly (≥65 year-old) and 25,264 matched non-elderly (25-64 year-old) depressed patients were created from a large national claims database of managed care plans from 2003 to 2006. Factors associated with ADT or PT were assessed using multivariate logistic models. During the 120 days following the depression diagnosis, the elderly persons were less often treated than the younger adults either by ADT (25.6% vs. 33.8%) or by PT (13.0% vs. 34.4%). ADT dispensing occurred later in the elderly group (51 vs. 14 days). ADT was associated with comorbid chronic conditions or polypharmacy in the elderly and younger adults. The selection of treatment (ADT or PT) was associated with the history of treated depression using the same type of treatment, in both groups. Thus, depression goes commonly untreated. Comorbidity was associated with higher ADT dispensing rates. However, although depressed elderly commonly presented with comorbidity, this age group was at higher risk of untreated illness or later treatment.

Comparing antidepressant treatment patterns in older and younger adults: a claims database analysis.

OBJECTIVES: To compare depressed older (≥65) and younger (25-64) adults with regard to antidepressant treatment patterns and to assess factors associated with 180-day nonpersistence. DESIGN: Retrospective matched cohort study. SETTING: U.S. managed care population. PARTICIPANTS: Older and matched younger adults diagnosed with depression and treated with antidepressants. MEASUREMENTS: Sociodemographic characteristics, comorbidities, polypharmacy, and characteristics of antidepressant treatment at 180 days were compared between older and younger adults. Analyses were conducted before and after the implementation of Medicare Part D on January 1, 2006, to consider the effect of this policy. RESULTS: Few participants received psychotherapy, especially older ones; rates were constant before and after 2006. Before 2006, older adults more frequently received antidepressants at lower (odds ratio (OR)=5.38, 95% confidence interval (CI)=3.57-8.13) or intermediate dose (OR=2.42, 95% CI=1.93-3.02) and had poorer adherence to treatment (P<.001) than younger adults. After 2006, older adults received similar proportions of intermediate or high antidepressant doses as younger adults, but a lower dosage was still more likely to be prescribed (OR=1.87, 95% CI=1.09-3.20) and had higher treatment adherence (P<.001). Medication profile did not significantly affect the risk of nonpersistence, but increased with lower antidepressant dose (P<.001). Whereas nonpersistence was higher in older adults before 2006 (hazard ratio (HR)=1.25, 95% CI=1.22-1.46), the trend reversed after 2006 (HR=0.76, 95% CI=0.66-0.88). CONCLUSION: More than half of participants with depression discontinued antidepressant treatment, and psychotherapy was rarely used. Implementation of Medicare Part D was associated with substantial changes in treatment of older adults with depression. The presence of comorbidities or polypharmacy was not associated with nonpersistence in depressed older adults.