To describe the emotions that primary care physicians (PCPs) and specialists in the United States (US) experience when their patients are diagnosed with a rare disease.

This study elicited humanistic burden of transfusion-dependent (TD) lower-risk (LR) myelodysplastic syndromes (MDS) on patients and their caregivers. US patients and caregivers were interviewed separately via telephone; patients were TD LR-MDS and received ≥2 red blood cell transfusions (RBCTs) in the past 4 months. Interviews assessed impacts of living with MDS and treatment burden from both patient and caregiver perspectives. Transcripts were coded to identify key themes. 8 patients and 8 caregivers (including 5 patient-caregiver pairs) were interviewed (median ages 73.5 [range, 58–87] and 63.0 [range, 30–85], respectively). Events leading to diagnosis included routine blood work and symptomatology, with the former event having a longer time to diagnosis (medians 4.5 years [range, 2 months–8 years] and 1 month [range, 1 month–1 month], respectively). Nearly all patients felt they had not received specific MDS information from physicians at diagnosis; frequently, patients were monitored and not treated following initial diagnosis. Patients and caregivers reported fatigue, shortness of breath, and dizziness as primary symptoms. Patients focused on impacts of MDS/RBCTs on emotions, social events, travel, physical activities, and relationships. Within pairs, caregivers appeared more likely to recognize patient-identified impacts on emotional health, e.g., depression, versus physical activity. RBCTs impose significant burden on patients and caregivers, who reported transfusions every 1 to 6 weeks, taking a median of 5.8 hours (range, 5.2–7.0), including travel, chair time, etc. Some expressed concerns about iron overload risk and potential major organ damage. Caregiver impacts included limiting physical and social events, less time with friends and family, and being unable to work. MDS has wide-ranging impacts on physical, emotional, and social well-being of patients and caregivers, with significant burden imposed by transfusion. Reducing transfusion dependence may alleviate the humanistic burden of TD LR-MDS on patients and caregivers.

Treatment patterns for surgically resected esophageal cancer (EC) and gastroesophageal junction cancer (GEJC) vary across Europe. This study describes real-world treatment patterns and outcomes for patients receiving surgery for stage II or III EC or GEJC. In this retrospective, non-interventional chart review, physicians in Europe (UK, France, Italy, Germany, Spain) were asked to provide clinical and treatment data about their EC and GEJC patients. Patients included were ≥18 years old and underwent surgical resection (index) of Stage II or III cancer between October 2017 and October 2018. Data were collected from medical records until death, loss to follow-up, or end of data collection (June 2020). 252 physicians reported data for 734 patients who received surgery for Stage II or III esophageal squamous cell carcinoma (ESCC) (21%), esophageal adenocarcinoma (EAC) (40%), or GEJC (39%). Patients had a mean age of 62.5 years, 80.4% were male, and 84.9% had an ECOG score of 0 or 1 at the time of diagnosis. Over two-thirds of patients received R0 resection (70.5%). For patients who received neoadjuvant therapy, 69.9% did not experience complete pathological response to treatment. The median (IQR) follow-up was 26.0 (18.0-31.0) months. Among the 734 patients, 66.3% (n=487) received neoadjuvant therapy, 31.5% (n=231) of which was neoadjuvant chemoradiotherapy (CRT), 28.3% (n=208) of which was neoadjuvant chemotherapy and 6.5% (n=48) of which was radiation alone. The most common neoadjuvant CRT regimens were cisplatin + 5-FU (26.4%) and carboplatin + paclitaxel (26.4%). The most common neoadjuvant chemotherapy regimens used were docetaxel + oxaliplatin + leucovorin + 5-FU (FLOT; 26%) and cisplatin + 5-FU (15.9). Cisplatin + 5-FU was more common in ESCC patients, while the FLOT regimen was more commonly used in GEJC and EAC patients. Following surgery, a majority of patients (54.1%) did not receive adjuvant therapy. For patients who received neoadjuvant CRT prior to surgery, less than 30 patients in each country received adjuvant treatment. For patients who received neoadjuvant chemotherapy prior to surgery, 50% also received chemotherapy after surgery. Of all included patients, 22.2% experienced locoregional or metastatic recurrence and 6.1% of patients died during the data collection period. Among those who recurred, the median time to recurrence was 6.0 (0.0-26.0) months. This real-world study showed that a majority of stage II/III EC/GEJC patients received neoadjuvant treatment prior to surgery, however, 69.9% still had residual disease (non-pathological complete response). After surgery, the majority of patients did not receive adjuvant treatment which is in line with clinical guidelines, and disease recurrence was common. These observations indicate a high unmet need in this patient population for more effective treatment options in the adjuvant setting.

Esophageal cancer is the 7th most common cancer in Spain, with an incidence of 2,383 cases per year. Patient with EC has significant unmet medical need, poor quality of life and low survival rates. A retrospective, non-interventional survey of 52 Spanish physicians was conducted between August-November 2018. Clinical data were collected from medical charts for patients aged ≥20 years who had initiated through completion or stopping 1/2 line treatment for ESCC and for esophageal adenocarcinoma or BSC at either line of therapy. Excluded were patients with adenosquamous carcinoma, or with Siewert type 1 gastroesophageal junction cancer . The 52 physicians surveyed were aged 46.5±11.44y , 71.2% male, 14.9±5.9y in practice, 93.4% hospital-based, and treated a median of 50 EC patients in the past 2 years. 149 patients were included, with mean age at 1L of 62.8±9.2y and 83.5% male. At diagnosis patients presented the following comorbidities: 28.9% hypertension, 27.5% hyperlipidemia, 23.5% diabetes, 14.8% dysphagia, and 14.1% chronic obstructive pulmonary disease. At 1L, 91.1% of EC patients received active systemic therapy (Cisplatin+5-FU=19.0%) and 8.1% received BSC (ESCC=5.1%; EAC=11.4%). In 2L (n=44), 81.8% (n=36) of EC patients received systemic treatment (docetaxel n=9; 25.0%) and 18.2% (n=8) received BSC (20.0% in EAC vs 16.7% in ESCC). Physician-reported treatment decisions based primarily on personal experience (35%) and side effects (65%). The main 2L treatment goals were extent patients' life (41.7%) and relieve symptoms (29.2%). For 2L ESCC patients, the most common grade 3 or 4 adverse events were fatigue (70%), neutropenia (55%) and anemia (50%). In this real-world survey of Spanish physicians, approximately 1/20 ESCC patients received BSC at 1L, whereas approximately 1/6 ESCC patients received BSC at 2L. Data indicated that physician treatment decision-making, treatment goals, and adverse events show a great unmet need for a more efficacious or a safer/better tolerated 2L ESCC treatment.

Sorafenib is indicated for the first-line (1L) treatment of HCC. This study examined physician attitudes towards treatment based on preferred 1L systemic therapy for advanced HCC. A retrospective, non-interventional study was conducted among 278 physicians in Canada, France, Germany, Italy, Spain, and the UK between February-March 2018. Physician attitudes, patient characteristics and treatment-related data were collected from medical charts of the 2-3 most recent HCC patients. Descriptive, bivariate, and Chi-Square Automatic Interaction Detection (CHAID) analyses were used to examine physician and patient data. The study surveyed physicians primarily from Europe (93%), aged 45.6±9.3 years with 72% male, and 89% hospital-based who provided information on 706 patients (n=504 sorafenib; n=202 other [83% chemotherapy; 10% targeted therapy; 7% checkpoint inhibitors]). Most physicians (80%) reported 1L sorafenib use regardless of country. Physician-reported attitudes indicated that 27% prescribed based on personal experience rather than clinical data, 90% agreed on an unmet need for more efficacious HCC treatments, 85% prescribed based on guidelines, and 54% were motivated to prescribe new therapies. Attitudes differed by physician group (sorafenib treaters vs. other only) regarding reasons for prescribing and an unmet need (p≤0.002). The most common primary treatment rationale was efficacy (58%) regardless of physician group, however guideline-based rationale was a stronger driver among physicians reporting patients with sorafenib 1L use compared to those reporting non-sorafenib 1L use only (24% vs. 8%, p<0.001). CHAID analysis supported these findings that physician characteristics and attitudes, in addition to patient characteristics, such as portal vein invasion and Child-Pugh score at diagnosis, predict treatment choice. HCC treatment choices appear to be influenced by physician and patient characteristics as well as physician attitudes. Understanding 1L HCC therapy determinants is important as the treatment landscape evolves to address unmet needs.

Esophageal cancer (EC) is the eighth most common cancer and the sixth common cause of cancer-related deaths worldwide. It is associated with a poor prognosis having an 18% 5-year overall survival. This study examined treatment patterns and HCRU in patients who initiated first line (1L) or second line (2L) systemic therapy for squamous cell carcinoma (ESCC) with a focus on 2L patients. A retrospective, non-interventional study was conducted among 639 physicians in the US, Canada, France, Germany, Italy, Spain, UK, Japan, Korea, Taiwan and China between September and October 2018. Patient characteristics and treatment-related data were collected from the 3 most recent patient medical charts. 1,049 ESCC patients were included (n=387 2L). The mean age was 65 years, 82% were male, 53% had gastroesophageal reflux disease, and 21% had Barrett’s Esophagus. Testing rates were: 51% for HER-2, 35% for MSI, and 28% for PD-L1. 59% of 2L patients were given systemic treatment and 41% best supportive care. Taxane monotherapy was preferred in Japan (62%), UK (50%), Germany (43%), Spain (40%) and Canada (40%). Most commonly reported grade 3-4 adverse events (AEs) for 2L patients were neutropenia (9%), fatigue (9%), nausea (8%), diarrhea (8%), and anorexia (8%). The rate of AE-related ER visits was 15% and hospitalizations was 13%, with a median length of stay among those with a hospitalization of 10.5 days. The percentage of 2L patients with an ECOG score 2-4 following treatment was 58%. Only 8% of patients went onto 3L; 38% of patients died after 2L, and 49% did not receive additional treatment at the time of data collection. Effective options for 2L treatment of ESCC are limited, resulting in poor ECOG performance status and high mortality and adverse event rates. This suggests a high unmet need for 2L patients.

Esophageal cancer (EC) is the seventh most common cancer and the sixth common cause of cancer-related deaths worldwide. Those with metastatic disease have a poor prognosis, with an 8% 5-year overall survival. This study examined treatment patterns and healthcare resource utilization (HCRU) in patients who initiated first-line (1L) or second-line (2L) systemic therapy or received best supportive care (BSC) for esophageal squamous cell carcinoma (ESCC) with a focus on differences by Asian versus Western countries in 2L. A global retrospective, non-interventional study was conducted among 639 physicians from Asian (Japan, Korea, Taiwan and China) and Western (US, Canada, France, Germany, Italy, Spain, UK) countries between September-October 2018. Patient characteristics and treatment-related data were collected from the 3 most recent patient medical charts for patients on 1L, 2L or BSC. Chi-square or Fisher's exact tests were used. 387 2L ESCC patients treated systemically or with BSC were profiled (West n=195; Asia n=192). The mean age was 63.4 years, and 81.4% were male with no differences by geography. Compared to Asia, Western patients were more likely to be current smokers (29.7% vs 13.5%; p=0.001), current alcohol users (31.8% vs 17.7%; p=0.002) and diagnosed as metastatic (58.5% vs 37.5%; p<0.001). At 2L, more Western patients received systemic treatment (West=63.6% vs Asia=52.6%; p=0.029) including a higher use of immunotherapy or targeted therapy (16.9% vs 3.0%; p=0.001). Taxane therapy use was similar across regions (West=42.7% vs Asia=48.5%, p=0.388), although lower rates were observed in the US (34.9%). HCRU for adverse events was lower in Western countries (e.g., ER visits=8.0% vs 22.2%; p<0.001). Following 2L systemic therapy 32.4% of patients died (West=33.1% vs Asia=31.7%; p=0.826). There are some differences in baseline characteristics and treatment patterns across regions with Western patients having more high-risk characteristics than Asian patients, but patient survival was similar.

HCC is the 9th most common cancer in Spain, with an incidence of 5,878 new cases per year. Patient with HCC has significant unmet medical need, poor quality of life and low survival rates. A retrospective, non-interventional survey of 52 Spanish physicians was conducted between February-March 2018. Clinical and treatment data were collected from medical charts for patients aged ≥18 (with Child-Pugh A/B status at 1L initiation), who initiated and completed systemic 1L treatment for HCC within 2y of data collection. Descriptive statistics compared 1L systemic therapy, sorafenib vs. other. The 52 physicians surveyed were aged.46.0±10.4y (mean±SD), 65.4% male, 14.3±5.6y in practice, 94.2% hospital-based, and treated a median of 30 aHCC patients in the past 2 years. 125 patients were included, with mean age at 1L of 65.3±10.4y and 84.0% male. Patients presented as follows at diagnosis: 62.4% portal vein invasion, 56.8% severe fibrosis or cirrhosis and 46.4% distant metastasis. Comorbidities: alcoholism (32.8%), Hepatitis C (16.0%), Hepatitis B (5.6%), nonalcoholic steatohepatitis or nonalcoholic fatty liver disease (7.4%). Physicians based HCC treatment decisions on: personal experience (38.5%), guidelines (78.9%), and over 90% believe there is a great unmet need for more efficacious aHCC treatment. Of these patients, 75.2% received with sorafenib and 24.8% were offered other treatments. Dose or schedule intensity was reduced significantly in 33.0% of patients receiving sorafenib vs. others 6.5% (p<0.001), and a difference was also shown for treatment duration (p=0.005). The most common grade 3 or 4 adverse events were fatigue (9.6%), hypertension (4.8%), and diarrhea (4.8%). In this Real World chart survey of Spanish physicians, sorafenib remains the most commonly used 1L systemic therapy for aHCC. Understanding determinants of 1L therapy is important as the treatment landscape of HCC is evolving to address unmet need.

Examine treatment patterns of patients receiving 2L treatment for mUC in Canada. A retrospective, non-interventional study was conducted among 25 Canadian physicians. Data were collected from medical charts of patients who started and stopped 2L treatment for mUC within 2 years of data collection. 2L was defined as treatment after progression/recurrence following first-line (1L) treatment, or recurrence ≤12 months of neoadjuvant/adjuvant treatment. 112 mUC patients with a mean age at diagnosis of 64.3±9.1 years and 81.3% were male were examined. Initial urothelial cancer diagnosis was metastatic (85.7%), with the primary tumor site being urinary bladder (76.8%), and primary tumor histology being transitional cell carcinoma (82.1%). 42.9% of patients had lung metastases. Most 1L patients received platinum-based combination treatment: gemcitabine + cisplatin (29.5%) or gemcitabine + carboplatin (22.3%). 61.6% of patients had complete or partial response to 1L treatment. At initiation of 2L treatment, 47.4% of patients had ECOG status Grade 0 or 1, and 34.8% had ECOG Grade 2. Although most patients (60.7%) were eligible for 2L platinum based treatment, 60.7% of 2L patients received non-platinum-based monotherapy treatment, with 36.3% of 2L patients receiving paclitaxel monotherapy. 39.3% of 2L patients received platinum-based combination treatment. Primary rationale for 2L treatment was treatment efficacy (58.0%), followed by safety (12.5%). Physicians who treated with platinum-based medication were five times more likely to base their decision on national guidelines compared to those choosing non-platinum-based therapy (22.7% vs 4.4%, respectively, p=.003). 60.7% percent of 2L Canadian patients received non-platinum-based monotherapy with 36.3% of 2L patients receiving paclitaxel monotherapy. Physicians report efficacy as the primary rationale for choice of 2L treatment. Information on 1L and 2L treatment is critical for understanding real world practice, while the introduction of immune checkpoint inhibitors offers new treatment options in the second-line setting.

HCC is the fifth-most common cancer worldwide and third-leading cause of cancer-related deaths. Patients with advanced HCC have a particularly poor prognosis and limited treatment options. This study examined treatment patterns and HCRU in patients who initiated first (1L) or second line (2L) systemic therapy for HCC. A retrospective, non-interventional study was conducted among 278 physicians in Canada, France, Germany, Italy, Spain and UK between February-March 2018. Patient characteristics and treatment-related data were collected from medical charts of the 2-3 most recent patients. Of the 706 patients treated with 1L therapy for HCC, 88% patients had advanced disease, with a median age of 63 years at 1L treatment, 79% were male, and 47% had severe fibrosis or cirrhosis (23% with status unknown). Comorbidities included alcoholism (33%), Hepatitis C (14%), Hepatitis B (10%), nonalcoholic steatohepatitis and/or nonalcoholic fatty liver disease (9%). Most patients (71%) received sorafenib at 1L therapy, 22% of patients received 2L systemic therapy and 3% received best supportive care following 1L therapy at chart abstraction. 89% of patients visited an oncologist at least once a month, with 39% visiting ≥2 times. 19% of patients received ≥1 scans/month. Most commonly reported grade 3-4 adverse events (AEs) at 1L were asthenia/fatigue (66 reports), diarrhoea (34), and hand-foot skin reaction (25). 46 1L patients were hospitalised for an AE, with median length of stay being 5.0 days as inpatient and 5 days as outpatient. In Canada and Europe, the most common 1L treatment in advanced HCC was sorafenib. HCRU for these patients was high. Prevalence of HBV/HCV and cirrhosis were lower than expected but this may be due to under-diagnosis or limitations of chart review. Poor treatment outcomes suggest a high unmet need for these patients.

To demonstrate the use of the Chi-square Automatic Interaction Detection (CHAID) analysis to identify drivers of second-line (2L) therapy for metastatic urothelial cancer (mUC). This study was a retrospective, non-interventional study conducted among n=295 physicians and n=1397 patients in Australia (n=18; n=71), Canada (n=25; n=112), France (n=52; n=247), Germany (n=49; n=244), Italy (n=50; n=248), Spain (n=50; n=241), and the UK (n=51; n=234). Patient characteristics, treatment patterns, and outcomes data were collected from medical charts of the 5 most recent patients who began and stopped 2L mUC treatment. 2L was defined as treatment after progression/recurrence after first-line (1L) treatment, or recurrence ≤12 months of neoadjuvant/adjuvant treatment. CHAID analysis was used to examine drivers related to receiving platinum versus non-platinum based 2L treatment. CHAID and other statistical anslyses were performed using SPSS v23. Physicians aged 45.0±8.2 years specializing primarily in oncology (93%) reported on data for 2L mUC patients. Most patients were male (74%) and aged 63.5±9.2 years at mUC diagnosis. Overall, 23.5% (n=328) of patients received platinum-based and 76.5% (n=1069) received non-platinum-based 2L mUC therapy. While, as expected, physician-reported patient platinum eligibility was correlated with treatment course (p<0.001), predictors of therapy type correlated differently within each eligibility groups (p≤0.02). For example, patients who were treated by younger physicians were less likely to receive platinum-based therapy (31.7% vs 45.9%, respectively, p≤0.001) indicating that physician characteristics are a potential source of variance associated with treatment choice. A small percentage of non-platinum eligible patients receive platinum-based 2L therapy (1.4%) which increases to 6.6% when the site of metastases was not in the lungs when first diagnosed with mUC (p=0.001). Multiple factors are involved in treatment choice for mUC related both to the treating physician and the patient. CHAID analysis is a useful tool for identifying associations between subgroups.

The primary objective was to understand the treatment patterns of patients receiving 2L therapy for mUC in Spain. This study was a retrospective, non-interventional study conducted using a panel of 50 Spanish physicians. Patient characteristics, treatment patterns, and outcomes data were collected from medical charts of the five most recent patients who began and stopped 2L mUC treatment. 2L was defined as treatment after progression/recurrence after 1L treatment, or recurrence with ≤12 months of neoadjuvant/adjuvant treatment. Analyses were conducted using descriptive statistics. Data were collected from 241 patients. Mean age at 2L treatment initiation was 63.5 (±9.04) years, and 81% were male. Initial urothelial cancer diagnosis was metastatic for 88% of patients, with the primary tumor site being urinary bladder (76%) and histology being transitional cell (80%). Most patients received platinum-based combination 1L treatment: gemcitabine + cisplatin (50%) and gemcitabine + carboplatin (24%). 60% of patients had complete or partial response to 1L treatment. At initiation of 2L treatment, 54% of patients had ECOG Grade 0 or 1. The most common 2L treatment was non-platinum-based monotherapy: vinflunine (41%) and paclitaxel (20%). At the end of 2L treatment, 29% of patients achieved a complete or partial response, 25% stable disease and 46% disease progression. Platinum-based treatments compared with non-platinum-based treatments were associated with significantly more hospital days for chemotherapy administration (p<.001) and more hospital days for monitoring/recovery (p=.002). Non-platinum-based treatments compared with platinum-based-treatments were associated with significantly shorter duration of time from end of 1L to start of 2L (p<.001), from the end of 2L to start of 3L (p=.005), and time on 2L treatment (p=.005). 10% of patients received third line treatment. In Spain, the most common 2L mUC treatment is non–platinum-based monotherapy. Poor 2L treatment outcomes indicate a high unmet need for these patients.