Treatment patterns and outcomes in patients with metastatic synovial sarcoma in France, Germany, Italy, Spain and the UK.

Aim: Describing the treatment patterns, outcomes by line of treatment (LOT), and healthcare resource utilization (HCRU) in patients with metastatic synovial sarcoma (mSS). Patients & methods: In this descriptive, non-interventional, retrospective cohort study, physicians from five European countries reported on patients with recent pharmacological treatment for mSS. Results: Among 296 patients with mSS, 86.1, 38.9 and 8.4% received 1 LOT (1L), 2 LOTs (2L) and 3+ LOTs (L3+), respectively. Common regimens were doxorubicin/ifosfamide-based (37.4%) for 1L and trabectedin-based for 2L (29.7%). For 1L, median time to next treatment was 13.1 and 6.0 months for living and deceased patients, respectively. Median OS was 22.0, 6.0 and 4.9 months in all patients, 2L and 3L, respectively. HCRU data showed median one inpatient hospital admission, 3 days in hospital and four outpatient visits yearly. Conclusion: This large-scale study documents high unmet needs in patients previously treated for mSS and for more effective therapies.

Meta-analysis of pazopanib and trabectedin effectiveness in previously treated metastatic synovial sarcoma (second-line setting and beyond).

Background: This study examined the efficacy/effectiveness of pazopanib and trabectedin in previously treated metastatic synovial sarcoma (mSS). Materials & methods: A literature search identified studies (2002-2019) reporting outcomes of pazopanib and trabectedin in previously treated mSS, including median overall survival (mOS) and overall response rate (ORR). A meta-analysis was conducted and sensitivity analyses examined outcomes by agent (pazopanib/trabectedin), study type (clinical trial [CT] or real-world [RW]) and sample size. Results: Sixteen studies were included (pazopanib: n = 7; trabectedin: n = 9). Pooled mOS was 10.4 months and was consistent across agents and in RW and CT (pazopanib: 10.3; trabectedin: 10.4; CT: 10.8; RW: 9.9). ORR results were more variable (pooled ORR: 14.7%). ORR was consistently higher for RW (17.7%) than for CT (9.5%) and for pazopanib (18.9%) compared with trabectedin (12.3%). Conclusion: Poor outcomes across agents and settings highlight a need for novel treatments with improved efficacy. This study serves as a benchmark for efficacy estimates in this rare disease.

Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma. SS frequently spreads to other locations, referred to as metastatic SS (mSS) and is associated with a high death rate. Patients treated with first-line chemotherapy (1L setting), may need further lines of treatment (≥2L setting), which commonly involve the drugs pazopanib and trabectedin. This study assessed how well pazopanib and trabectedin work in people with ≥2L mSS, by examining both clinical trial (CT) and real-world (RW) studies. Overall, findings across 16 studies showed that mSS patients lived approximately 10 months after treatment with pazopanib or trabectedin in the ≥2L setting, and this was similar across both agents (10.3 months for pazopanib; 10.4 months for trabectedin) and between the CT (10.8 months) and the RW (9.9 months) settings. In terms of response to treatment, a higher percentage of people appeared to respond in RW settings (17.7%) than in CTs (9.5%), and to pazopanib (18.9%) compared with trabectedin (12.3%). These results show there is a need for better treatments for patients with previously treated mSS. These findings are useful benchmarks for the development of future treatment approaches for this rare disease.

Treatment patterns and outcomes in metastatic synovial sarcoma: a real-world study in the US oncology network.

Aim: To examine and understand patient characteristics, treatment patterns and outcomes for patients with metastatic synovial sarcoma (mSS) treated in a US community setting. Materials & methods: Retrospective observational study in adults with mSS in The US Oncology Network (diagnosed January 2012-December 2018). Results: Of 202 patients diagnosed with synovial sarcoma (SS), 71 had mSS. Of 39 patients with mSS who received first-line (1L) systemic treatment, 25 and 16 continued to 2L and 3L+ treatment, respectively. With each subsequent treatment line, time-to-treatment-discontinuation (1L-3L: 3.9-2.7 months) and time-to-next-treatment (1L-3L: 9.3-4.6 months) decreased. At 1L, median overall survival was 24.5 months. Conclusion: This study highlights the ongoing need for effective therapies for mSS.

Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma (STS), a group of rare cancers that start in the soft tissues, such as muscle, tendons, fat, lymph and blood vessels and nerves. Usually STS presents in one location, and frequently spreads to other locations, referred to as metastatic SS (mSS). Many studies have explored the characteristics, treatments and outcomes of people with STS. Yet, a limited number of studies have been performed specifically for people with mSS. This study aims to describe characteristics, treatment patterns and clinical outcomes of people with mSS treated in a US community setting. The study showed that more than a third of people diagnosed with SS had disease that spread, mostly to the lung. Of the 71 people with mSS included in the analysis, 39 people received chemotherapy. Of these, 25 people with mSS needed second-line chemotherapy and a further 16 people with mSS required third-line treatment. People with mSS who did not respond well to chemotherapy received a variability of treatments in the US community setting. More lines of treatment were associated with shorter time-to-next-treatment and reduced survival time. Together, these findings highlight the burden of illness and the need for more effective treatments for people with this rare disease. Investigating the characteristics, treatment patterns and clinical outcomes of people with mSS can help to understand the unmet need in this population and pave the way to improving future treatment approaches.

Qualitative study to characterize patient experience and relevance of patient-reported outcome measures for patients with metastatic synovial sarcoma.

BACKGROUND: The outlook for patients with metastatic synovial sarcoma (mSS) is poor. Better understanding of patient experience in this setting, beyond clinical measures, may guide improvements in management. Validated patient-reported outcome (PRO) instruments specific to many types of cancer exist, but for rare cancers this is often not the case. METHODS: This study aimed to characterize patient experiences of symptoms and impacts of mSS and evaluate the content validity and relevance of the novel European Organization for Research and Treatment of Cancer Item Library 31 (EORTC IL31) Disease Symptoms PRO tool assessing synovial sarcoma symptoms. This tool comprises items from preexisting, validated cancer-specific PRO instruments from the EORTC Item Library. It was developed as an mSS-specific add-on to the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30), which evaluates general cancer and treatment-related symptoms and functioning. This was a non-interventional, qualitative interview study involving semi-structured, concept elicitation (CE) and cognitive debriefing (CD) telephone interviews in adults with mSS. CE explored symptoms and their impact on functioning and quality of life; CD assessed participant understanding and relevance of the PRO tools. RESULTS: Among the 8 participants, the most common disease-related symptoms reported during CE were fatigue and pain, while shortness of breath was one of the most bothersome. The greatest negative impacts of mSS occurred in domains of physical functioning and sleep. Key treatment priorities for patients were to improve disrupted sleep and ability to undertake strenuous activities. CONCLUSIONS: The interviews showed that, when used together, the EORTC IL31 and EORTC QLQ-C30 covered symptoms and impacts of most relevance and importance to patients with mSS, with no notable gaps and good conceptual coverage. This study therefore supports the content validity of 2 tools in mSS, advocating their use in clinical trials to assess treatment impact on PRO measures of importance to these patients.

The Short- and Long-Term Burden of Acute Pancreatitis in the United States: A Retrospective Cohort Study.

OBJECTIVES: This retrospective cohort study assessed short- and long-term economic, clinical burden, and productivity impacts of acute pancreatitis (AP) in the United States. METHODS: United States claims data from patients hospitalized for AP (January 1, 2011-September-30, 2016) were sourced from MarketScan databases. Patients were categorized by index AP severity: severe intensive care unit (ICU), severe non-ICU, and other hospitalized patients. RESULTS: During index, 41,946 patients were hospitalized or visited an emergency department for AP. For inpatients, median (interquartile range) AP-related total cost was $13,187 ($12,822) and increased with AP severity (P < 0.0001). During the postindex year, median AP-related costs were higher (P < 0.0001) for severe ICU versus severe non-ICU and other hospitalized patients. Hours lost and costs due to absence and short-term disability were similar between categories. Long-term disability costs were higher (P = 0.005) for severe ICU versus other hospitalized patients. Factors associated with higher total all-cause costs in the year after discharge included AP severity, length of hospitalization, readmission, AP reoccurrence, progression to chronic pancreatitis, or new-onset diabetes (P < 0.0001). CONCLUSIONS: An AP event exerts substantial burden during hospitalization and involves long-term clinical and economic consequences, including loss of productivity, which increase with index AP event severity.

Risk of hospitalization for common neonatal morbidities in preterm and term infants: assessing the impact of one or more major congenital anomalies.

OBJECTIVE: To analyze the impact of ≥1 major congenital anomaly (CA) on risk and hospitalization for common neonatal morbidities. STUDY DESIGN: Retrospective infant cohort: 241,033 preterm and 3,446,156 term singletons in the US Premier Healthcare database (2006-2013) with up to 1-year follow-up. Discharge records were searched for ≥1 CA and neonatal morbidities. RESULTS: Five morbidities demonstrated strong increasing rates as GA decreased. RRs in preterm infants with CAs relative to those without CAs were: RDS (2.17, 95% CI 2.14-2.21), sepsis (2.42, 95% CI 2.37-2.46), apnea (2.04, 95% CI 2.01-2.07), infectious diseases (2.37, 95% CI 2.34-2.41), and hyperbilirubinemia (1.25, 95% CI 1.24-1.26). Median length of NICU stay (days) was consistently longer in infants with ≥1 CA relative to infants without CA during each GA period. CONCLUSIONS: Preterm infants with ≥1 major CA have increased risk of hospitalization for common morbidities, implying compromised neonatal health regardless of CA type.

The cost of preterm labor and preterm birth for mothers with uncomplicated pregnancies and their infants in Italy: a retrospective cohort study.

BACKGROUND: Preterm labor (PTL)/preterm birth (PTB) impose significant burden on health-care systems. Women with uncomplicated pregnancies at risk of PTL/PTB have not been widely investigated, and published evidence on the costs of these women and their infants in Italy is absent. We aimed to describe women with uncomplicated pregnancies and associated costs for these women and their infants. METHODS: Data on women aged 12-44 years with uncomplicated pregnancies who delivered between 1 September 2009 and 31 December 2014 with PTL diagnosis alone or PTL and PTB were included from four Italian databases. Costs were examined during pregnancy, delivery, and 3 years after delivery for mothers and infants, overall and by gestational age (GA). RESULTS: A total of 3058 mothers linked to 3333 infants were included. Costs during pregnancy were €1777. Costs during delivery for PTL/PTB mothers and their infants ranged from €3174 (GA ≥37) to €21007 (GA <28). Combined maternal and infant costs appeared higher for births with lower GAs (<37) in the three-year follow-up. CONCLUSIONS: In Italy, PTL/PTB mothers with uncomplicated pregnancies with infants at lower GAs appeared to incur higher medical costs compared to mothers with infants at higher GAs in all three time periods, with particularly marked differences found when considering mother and infant combined costs.

Short and long-term costs among women experiencing preterm labour or preterm birth: the German experience.

BACKGROUND: Preterm labour and birth (PTL/PTB) is characterised by major health and developmental risks for children, life-changing consequences for their families, and substantial healthcare and economic challenges for wider society. While it is known that PTL/PTB impacts infant healthcare costs in the short and long term in Germany, maternal costs have not been described in detail. The aim of this study was to comprehensively describe costs and resource use among PTL/PTB mothers during pregnancy, at hospitalisation for delivery, and up to three years after delivery-overall and according to gestational age (GA) at delivery. METHODS: This study used data from the Statutory Health Insurance (SHI) sample of the AOK Hessen database in Germany. Mothers aged 12-44 years with deliveries between 2009 and 2013 and > 9 months of medical history prior to delivery were included. PTL/PTB mothers were defined by an International Classification of Diseases, 10th Revision (ICD-10) code for PTL during pregnancy, a diagnosis-related group (DRG) code indicating birthweight < 2500 g, or delivery of an infant < 37 weeks GA. Inpatient and outpatient resource use and total direct medical costs were examined during pregnancy, at delivery hospitalisation, and up to three years post-delivery. RESULTS: Of all mothers, 2147 (20%) experienced PTL/PTB. During pregnancy, median costs for PTL/PTB mothers were €2130. During delivery hospitalisation, the mean length of stay for all PTL/PTB mothers was 6.0 days, and median costs were €2037. Length of stay and costs declined with increasing GA. Long term, PTL/PTB mothers' total median costs were €607 in Year 1, €332 in Year 2, and €388 in Year 3 post-delivery. In each year after delivery, median costs appeared to be greater for mothers who delivered at lower GAs. CONCLUSION: In this description of costs and resource use among PTL/PTB mothers in Germany throughout the pregnancy and up to three years after delivery, the greatest costs were noted prior to delivery. Costs appeared to decrease with increasing GA, particularly during the delivery hospitalisation and the first year after delivery.

Experience of Symptoms and Disease Impact in Patients with Adenomyosis.

BACKGROUND: Adenomyosis is a poorly understood, benign disease of the uterus. OBJECTIVE: In this study, patient interviews were conducted to characterize the symptoms and impact of adenomyosis. METHODS: This was a cross-sectional study in which women with adenomyosis were recruited from five US clinics and a health-related social network forum. Participants (aged 18-55 years) were pre-menopausal with a history of regular menstrual cycles. Participants were interviewed about their experiences with adenomyosis, symptoms and impacts on day-to-day activities (concept elicitation), and subsequently about the occurrence, relative severity, and impact of symptoms (card-sorting exercise). RESULTS: In total, 31 women were interviewed. Mean duration since onset of first adenomyosis symptom was 5.7 years; 41.9% reported severe/very severe adenomyosis. Over 50 symptoms and 30 impacts of adenomyosis were reported in the concept elicitation; 87% of symptoms were reported after 7 interviews and 78% of impacts after 5 interviews, indicating a condition with a significant symptom burden and a consistent presentation. The most common symptoms were heavy menstrual bleeding (87%), cramps (84%), and blood clots during menstrual bleeding (84%). The most common impacts were burdensome self-care hygiene (71%), and fatigue/low energy (71%). In the card-sorting exercise, the most commonly endorsed symptoms were pain during menstruation/menstrual cramps and heavy menstrual bleeding (both frequently rated as severe). The symptom with the highest impact was heavy menstrual bleeding. CONCLUSION: Initiatives to understand women's experiences with adenomyosis may improve management of the condition. This study provides a first step in understanding their experience and new information on the symptom profile of adenomyosis.

Increasing economic burden of tyrosine kinase inhibitor treatment failure by line of therapy in chronic myeloid leukemia.

OBJECTIVE: To assess the economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML), by assessing all-cause health care resource use (HCRU) and costs in the year after treatment failure by line of therapy (LOT; 1L/2L/3L) using real-world data. METHODS: Treatment episodes initiating a TKI of interest (index TKI) during June 2008-December 2011 were identified from the IMS PharMetrics Plus Health Plan Claims Database for adult patients with CML diagnosis (ICD-9-CM 205.1x), 120 days pre-index continuous enrollment (CE) and no clinical trial participation. Episodes experiencing treatment failure, defined as switch to a non-index TKI or discontinuation of index TKI (gap of ≥ 60 days), and with 1 year CE post-failure, were analyzed. LOT was determined by number of unique TKIs used in the pre-index. All-cause HCRU and costs (2012 USD) in the 1 year post-failure were assessed by LOT, and the comparisons between 1L and 2L failures were also adjusted using multivariate generalized linear models (GLMs) to control for underlying differences. RESULTS: A total of 706 episodes were identified (518 1L; 180 2L; 8 3L). Unadjusted HCRU over 1 year post-failure increased significantly. This was accompanied by a significant increase in unadjusted mean costs for 2L failures vs. 1L failures ($99,624 vs. $78,667, p = 0.021, Δ$20,957). Following the adjustment using GLMs, adjusted mean costs were 38% higher (95% CI 1.14-1.68), driven primarily by use of medical services. In adjusted analyses, compared to 1L, 2L failures had: 45% more ambulatory visits (mean 31 vs. 21, 95% CI 1.26-1.66), 75% higher risk of hospitalization (33% vs. 23% hospitalized, 95% CI 1.16-2.64), and 73% higher medical costs (95% CI 1.31-2.29). Medical costs comprised a greater proportion of total costs in 2L vs. 1L (55% vs. 44%); pharmacy costs did not increase significantly. CONCLUSIONS: The economic burden over 1 year post TKI failure increased with each sequential line of TKI treatment failure.

Economic Burden of Tyrosine Kinase Inhibitor Treatment Failure in Chronic Myeloid Leukemia.

BACKGROUND: The economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML) is not well understood. The objective of this study was to quantify the economic burden associated with treatment failure versus successfully remaining on TKI therapy. METHODS: Treatment episodes for adult CML patients initiating a TKI of interest (imatinib, dasatinib, or nilotinib; index TKI) during July 1, 2008, to December 31, 2011, with continuous enrollment for ≥ 120 days before and 1 year after the initiation were identified from the IMS PharMetrics Plus Health Plan Claims Database. Eligible episodes of TKI treatment failure were matched to those without failure using propensity scores based on patients' baseline demographic and clinical characteristics. Treatment failure was defined as a switch to a nonindex TKI or discontinuation (gap in pharmacy claims ≥ 60 days) of index TKI over the 1-year follow-up. Mean all-cause health care resource utilization and costs per episode (in 2012 US dollars) over follow-up were compared between failures and nonfailures. RESULTS: Among 1774 eligible episodes, 547 failures were matched to 547 nonfailures. Failures had fewer TKI prescription fills but higher utilization of all other services versus nonfailures. Consequently, failures incurred lower pharmacy costs ($51,238 vs. $72,450; Δ-$21,212) but higher medical costs ($52,619 vs. $18,180; Δ$34,439) than nonfailures, resulting in higher total costs ($103,857 vs. $90,630; Δ$13,227) (all P < .05). CONCLUSION: Total health care costs are higher for episodes of TKI treatment failure than those of ongoing treatment, largely as a result of costly medical (nonpharmacologic) services. Avoiding treatment failure by optimal CML management may reduce health care costs.

Sex differences in ambulatory visits for chronic obstructive pulmonary disease, based on the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 1995 to 2004.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a rapidly growing public health problem in the United States. It is unclear whether men and women differ in their utilization of ambulatory care or medications prescribed for COPD. OBJECTIVE: To evaluate sex-related trends in physician-office and out-patient department COPD visits from 1995 through 2004. METHODS: We pooled data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) to derive national estimates of out-patient ambulatory COPD visits. For trend analysis we stratified the data into 2-year periods and by sex. The main variables of interest were the number of out-patient visits for COPD, patient characteristics, comorbidities, and medications prescribed. RESULTS: From 1995 to 2004, COPD-related out-patient visits increased among women and men; oral corticosteroids and short-acting bronchodilators were the most commonly prescribed drugs for both women and men; and prescriptions for inhaled corticosteroid decreased in both women (from 20% to 11%) and men (from 20 to 17%). In 2004, women surpassed men in out-patient COPD visits. CONCLUSIONS: COPD visits increased among both sexes, but the upward trend in COPD visits among women indicates that COPD is no longer a male-dominated disease. Providers should be aware of this shift in patient demographics and the differences between the sexes in COPD management.