Survival, treatment patterns, and costs of HER2+ metastatic breast cancer patients in Ontario between 2005 to 2020.

BACKGROUND: To enable the integration of novel therapies, it is critical to understand current long-term outcomes in HER2-positive metastatic breast cancer (mBC), including survival, treatment patterns, and costs. We sought to define these outcomes among patients with mBC in Ontario. METHODS: We conducted a retrospective population-level study in Ontario women diagnosed with breast cancer of any stage between January 1, 2005 and December 31, 2019, with follow-up until December 31, 2020. HER2-positivity was based on receipt of a HER2-targeted therapy (HER2-TT) in the first line (1L) metastatic setting. Administrative databases at ICES were used to assess outcomes. RESULTS: In Ontario, 2557 patients were diagnosed with mBC and received a HER2-TT, and of these 1606 were diagnosed with early-stage (stage I-III) that became metastatic (recurrent), while 951 were diagnosed with late stage/de novo mBC (stage IV). The average age of all patients was 54.8 years ± 12.7 years. Treatment regimens that included pertuzumab and trastuzumab (cohort name: pert_tras) were the most frequently used HER2-TT for 1L mBC (51.4%), while T-DM1 was the most frequent therapy (87.5%) in second line (2L). The median overall survival (mOS) from initiation of 1L pert_tras was not reached, whereas mOS from initiation of T-DM1 in 2L was 18.7 months. The overall mean cost per patient on pert_tras during 1L was $267,282. The main cost drivers were the cost of systemic therapy, followed by cancer clinic visits, with a mean cost per patient at $158,961 and $73,882, respectively. CONCLUSION: The baseline characteristics and treatment patterns for patients who received HER2-TT in our study align with previously reported results. However, the mOS observed for 2L T-DM1 was shorter than that found in pivotal, clinical trial literature. As expected, anti-cancer systemic therapy costs were the main contributor to the over quarter-million dollar mean cost per patient on pert_tras in 1L.

Describing the resource utilisation and costs associated withvertebral fractures: the Build Better Bones with Exercise (B3E) Pilot Trial.

This analysis examined costs/resources of 141 women with vertebral fractures, randomised to a home exercise programme or control group. Total, mean costs and the incremental cost-effectiveness ratio (ICER) were calculated. Quality of life was collected. Cost drivers were caregiver time, medications and adverse events (AEs). Results show adding an exercise programme may reduce the risk of AEs. INTRODUCTION: This exploratory economic analysis examined the health resource utilisation and costs experienced by women with vertebral fractures, and explored the effects of home exercise on those costs. METHODS: Women ≥ 65 years with one or more X-ray-confirmed vertebral fractures were randomised 1:1 to a 12-month home exercise programme or equal attention control group. Clinical and health system resources were collected during monthly phone calls and daily diaries completed by participants. Intervention costs were included. Unit costs were applied to health system resources. Quality of life (QoL) information was collected via EQ-5D-5L at baseline, 6 and 12 months. RESULTS: One hundred and forty-one women were randomised. Overall total costs (CAD 2018) were $664,923 (intervention) and $614,033 (control), respectively. The top three cost drivers were caregiver time ($250,269 and $240,811), medications ($151,000 and $122,145) and AEs ($58,807 and $71,981). The mean cost per intervention participant of $9365 ± $9988 was higher compared with the mean cost per control participant of $8772 ± $9718. The mean EQ-5D index score was higher for the intervention participants (0.81 ± 0.11) compared with that of controls (0.79 ± 0.13). The differences in quality-adjusted life year (QALY) (0.02) and mean cost ($593) were used to calculate the ICER of $29,650. CONCLUSIONS: Women with osteoporosis with a previous fracture experience a number of resources and associated costs that impact their care and quality of life. Caregiver time, medications and AEs are the biggest cost drivers for this population. The next steps would be to expand this feasibility study with more participants, longer-term follow-up and more regional variability.

Examining the medical resource utilization and costs of relapsed and refractory chronic lymphocytic leukemia in Ontario.

PURPOSE: The purpose of the present study was to collect medical resource utilization data and costs in Ontario for the management of patients with relapsed or refractory chronic lymphocytic lymphoma (cll) who have undergone at least 1 treatment course and have been stratified by Rai staging. METHODS: This retrospective longitudinal cohort study, conducted by chart review, analyzed anonymized patient records from two cancer centres in Ontario. Comprehensive records of 86 patients meeting the inclusion criteria were used to obtain resource utilization, which, multiplied by unit costs, were used to determine overall and mean costs. Descriptive statistics are presented for patient demographics, medical resource utilization, and costing data. RESULTS: The total cost for the cohort was $2.2 million over a mean follow-up period of 4.7 years. The mean total cost per patient (regardless of follow-up) was $25,736. In terms of Rai staging, overall mean costs were highest for stage iv patients. Almost 50% of the total cost was attributable to cll treatments, among which fludarabine-based treatments had the highest utilization. CONCLUSIONS: For this Canadian cll cohort, medical resource utilization and costs were determined to be $2.2 million, with cll treatments accounting for about half the cost. Costs generally increased with Rai stage.

Resource utilization and costs of managing patients with advanced melanoma: a Canadian population-based study.

BACKGROUND: The use and detailed costs of services provided for people with advanced melanoma (amel) are not well known. We conducted an analysis to determine the use of health care services and the associated costs delineated by relevant attributable costs, which we defined for subjects in the province of Ontario. METHODS: Through the Ontario Cancer Data Linkage Project, a cohort of amel patients with diagnoses between 31 August 2005 and 2012 (follow-up to 2013) and with valid International Classification of Diseases (9th revision, Clinical Modification) 172 codes and histology codes was identified. A cohort of individuals with amel having a combination of at least 1 palliative, 1 medical oncology, and 1 hospitalization code was generated. The health system services used by this population were clustered into hospitalization, palliation, physician medical visits, medication, homecare, laboratory, diagnostics, and other resources. Overall rates of use and disaggregated costs were determined by phase of care for the entire cohort. RESULTS: The mean age for the 2748 individuals in the cohort was 67 years. The greater proportion of the patients were men (65.6%) and were more than 65 years of age (>50%). In this advanced cohort, fewer than 45% of patients were alive 3 years after the malignant melanoma diagnosis. The average annual cost per patient over the time horizon was $6,551. At $15,830, year 1 after diagnosis was the most expensive, followed by year 2, at $8,166. CONCLUSIONS: Our data provide a baseline for the costs associated with amel treatment. Future studies will include newer agents and comparative effectiveness research for personalized therapies.

Radiation costing methods: a systematic review.

OBJECTIVE: Costs for radiation therapy (rt) and the methods used to cost rt are highly diverse across the literature. To date, no study has compared various costing methods in detail. Our objective was to perform a thorough review of the radiation costing literature to identify sources of costs and methods used. METHODS: A systematic review of Ovid medline, Ovid oldmedline, embase, Ovid HealthStar, and EconLit from 2005 to 23 March 2015 used search terms such as "radiation," "radiotherapy," "neoplasm," "cost," " cost analysis," and "cost benefit analysis" to locate relevant articles. Original papers were reviewed for detailed costing methods. Cost sources and methods were extracted for papers investigating rt modalities, including three-dimensional conformal rt (3D-crt), intensity-modulated rt (imrt), stereotactic body rt (sbrt), and brachytherapy (bt). All costs were translated into 2014 U.S. dollars. RESULTS: Most of the studies (91%) reported in the 33 articles retrieved provided rt costs from the health system perspective. The cost of rt ranged from US$2,687.87 to US$111,900.60 per treatment for imrt, followed by US$5,583.28 to US$90,055 for 3D-crt, US$10,544.22 to US$78,667.40 for bt, and US$6,520.58 to US$19,602.68 for sbrt. Cost drivers were professional or personnel costs and the cost of rt treatment. Most studies did not address the cost of rt equipment (85%) and institutional or facility costs (66%). CONCLUSIONS: Costing methods and sources were widely variable across studies, highlighting the need for consistency in the reporting of rt costs. More work to promote comparability and consistency across studies is needed.

Monthly blood transfusions decrease after four months of azacitidine.

BACKGROUND AND OBJECTIVES: Azacitidine (AZA) improves overall survival and transfusion independence in patients with myelodysplastic syndrome (MDS). We aimed to quantify the reduction in red blood cell (RBC) transfusions and to determine when this reduction occurs, in MDS patients treated with AZA. MATERIALS AND METHODS: We performed a retrospective audit of changes in RBC transfusion burden in 51 patients with predominantly higher risk MDS (26.5% high risk, 51.0% intermediate-2) who received AZA. Transfusion requirements were audited 6 months prior to and up to 18 months after therapy initiation, and data were analysed using a generalized linear mixed model. RESULTS: At baseline, 30 patients (58.8%) were transfusion dependent (TD). Seventeen patients (56.7%) achieved transfusion independence (TI) by 18 months, and 8 of these patients (47.1%) achieved this response by 4 months on therapy. Achievement of TI was not consistently durable in these 17 patients, as 11 patients reverted to TD while on therapy. Meanwhile, 6 of 21 patients who were TI at baseline became TD on therapy. The monthly average of RBC units transfused decreased significantly beginning at 4 months, with a reduction from 2.50 units per month at baseline to 1.00 units per month at month 4. This 60% reduction was significant (P = 0.002) and sustained beyond 12 months. CONCLUSION: These results bolster the notion that AZA significantly reduces transfusion burden and resource utilization and illustrate the limitations of the current WHO erythroid response criteria which do not account for differing durability and fluctuations of response.

A population-based study of the epidemiology of pancreatic cancer: a brief report.

OBJECTIVE: Administrative data are used to describe the pancreatic cancer (pcc) population. The analysis examines demographic details, incidence, site, survival, and factors influencing mortality in a cohort of individuals diagnosed with pcc. METHODS: Incident cases of pcc diagnosed in Ontario between 1 January 2004 and 31 December 2011 were extracted from the Ontario Cancer Registry. They were linked by encrypted health card number to several administrative databases to obtain demographic and mortality information. Descriptive, bivariate, and survival analyses were conducted. RESULTS: During the period of interest, 9221 new cases of pcc (4548 in men, 4673 in women) were diagnosed, for an age-adjusted standardized annual incidence in the range of 8.6-9.5 per 100,000 population. Mean age at diagnosis was 70.3 ± 12.5 years (standard deviation). Five-year survival was 7.2% (12.8% for those <60 years of age and 3.6% for those >80 years of age). Survival varied by sex, older age, rural residence, lower income, site of involvement in the pancreas, and presence of comorbidity. CONCLUSIONS: The mortality rate in pcc is exceptionally high. With an increasing incidence and a mortality positively associated with age, additional support will be needed for this highly fatal disease as demographics in Ontario continue to trend toward a higher proportion of older individuals.

Population-based utilization of radiation therapy by a Canadian breast cancer cohort.

We examined trends in radiation therapy (rt) utilization by a population-based breast cancer cohort in Ontario. The provincial cancer registry provided a breast cancer cohort based on diagnosis dates from April 1, 2005, to March 31, 2010. Staging information was also available. The cohort was then linked, by encrypted health card number, to linkable administrative datasets, including rt utilization. The average age in the identified female breast cancer cohort (n = 39,656) was 61.6 ± 14.0 years. Almost two thirds of the patients (n = 25,225) received rt, and staging information was available for 22,988 patients (9541 stage i, 8516 stage ii, 4050 stage iii, and 881 stage iv). The average number of rt courses received by the patients was 1.4 ± 0.7 for stage i, 1.8 ± 1.1 for stage ii, 2.5 ± 1.3 for stage iii, and 2.8 ± 2.4 for stage iv. The ratio of conventional rt to intensity-modulated rt was 70.9%:16.6% for stage i, 71.6%:11.3% for stage ii, 74.6%:4.6% for stage iii, and 89.6%:2.2% for stage iv. From 2005 to 2010, almost two thirds of a Canadian female breast cancer cohort received rt, and the average number of courses increased with disease severity. A similar trend was observed with the type of rt (use of conventional rt increased with disease severity). The next step is to apply unit costs to the number of fractions and to obtain rt planning and radiation therapist times.

Health system costs for stage-specific breast cancer: a population-based approach.

OBJECTIVE: The objective of the present analysis was to determine the publicly funded health care costs associated with the care of breast cancer (bca) patients by disease stage. METHODS: Incident cases of female invasive bca (2005-2009) were extracted from the Ontario Cancer Registry and linked to administrative datasets from the publicly funded system. The type and use of health care services were stratified by disease stage over the first 2 years after diagnosis. Mean costs and costs by type of clinical resource used in the care of bca patients were compared with costs for a matched control group. The attributable cost for the 2-year time horizon was determined in 2008 Canadian dollars. RESULTS: This cohort study involved 39,655 patients with bca and 190,520 control subjects. The average age in those groups was 61.1 and 60.9 years respectively. Most bca patients were classified as either stage i (34.4%) or stage ii (31.8%). Of the bca cohort, 8% died within the first 2 years after diagnosis. The overall mean cost per bca case from a public payer perspective in the first 2 years after diagnosis was $41,686. Over the 2-year time horizon, the mean cost increased by stage: i, $29,938; ii, $46,893; iii, $65,369; and iv, $66,627. The attributable cost of bca was $31,732. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. CONCLUSIONS: Costs of care increased by stage of bca. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. These data will assist planning and decision-making for the use of limited health care resources.

Retrospective cohort study of unresectable stage III non-small-cell lung cancer in Canada.

Background: The management of unresectable stage iii non-small-cell lung cancer (nsclc) is complex and best determined through multidisciplinary consultation. A longitudinal, population-level study was carried out to describe the management approach and outcomes of treatment in the real-world setting in Ontario. Methods: Individuals diagnosed with nsclc between 1 April 2010 and 31 March 2015 were identified in the Ontario Cancer Registry. Unresectable disease was defined as no surgery reported within 3 months of diagnosis. Initial treatments included radiotherapy (rt, curative or palliative), chemotherapy, targeted therapy, and chemoradiation [crt, concurrent (ccrt) or sequential (scrt)]. Survival was calculated from diagnosis with stage iii disease to death or last follow-up. Results: Of the 24,729 individuals diagnosed with nsclc, 5243 (21.2%) had stage iii disease, with most of the latter group (4542, 86.6%) having unresectable disease. Median age was 70 years, and 54.2% were men. The frequency of first-line treatment was ccrt, 22.1%; palliative rt, 21.0%; curative rt, 19.6%; no treatment, 19.6%; chemotherapy alone, 11.6%; scrt, 5.4%; and targeted therapy, 0.7%. Median overall survival (mos) was 14.2 months [95% confidence interval (ci): 13.6 months to 14.7 months], with the longest survival observed in patients who received targeted therapy (mos: 34.7 months; 95% ci: 21.4 months to 51.2 months), and the poorest, in those receiving no cancer treatment (mos: 5.9 months; 95% ci: 5.0 months to 6.4 months). The mos in patients receiving ccrt was 23.6 months (95% ci: 21.4 months to 25.6 months). Conclusions: Guideline-recommended ccrt is undertaken in only a small proportion of patients with unresectable nsclc in Ontario. The reasons for low uptake of that recommendation are only partly understood.

Real-world treatment patterns and survival in stage IV non-small-cell lung cancer in Canada.

Background: Almost half of all patients with non-small-cell lung cancer (nsclc) present with stage iv disease. The objective of the present study was to characterize treatment patterns and survival outcomes in patients with advanced nsclc. Methods: We conducted a longitudinal population-level study in patients diagnosed with stage iv nsclc in Ontario between 1 April 2010 and 31 March 2015, with follow-up to 31 March 2017 for overall survival and treatment sequence. Patients were stratified as nonsquamous or squamous histology. A sub-analysis was conducted for patients with nonsquamous histology who received targeted therapies, on the assumption that their tumours were EGFR mutation-positive (EGFRm+). Treatment patterns were determined, and survival was calculated from date of diagnosis to death or censoring. Results: Of 24,729 nsclc cases identified, stage iv disease was diagnosed in 49.2%, histology was nonsquamous in 10,103, and EGFRm+ was assumed in 508. Median patient age ranged from 69 to 72 years for the three cohorts. For patients with nonsquamous histology, palliative radiotherapy was the most frequently used first-line treatment (44.4%), followed by no treatment (26.7%) and chemotherapy (14.9%). In the EGFRm+ cohort, 75.6% received gefitinib as first- or second-line therapy, and almost half (47.4%) the 473 patients with squamous histology treated with first-line chemotherapy received cisplatin or carboplatin with gemcitabine. Median overall survival in the nonsquamous and squamous cohorts was 4.9 and 4.6 months respectively; it was 17.6 months for patients who were EGFRm+. Conclusions: Survival of patients with stage iv nsclc remains poor, with the exception of patients who are EGFRm+. Only 14.9% of patients received first-line chemotherapy; the mainstay of treatment was palliative radiotherapy.

A population-based analysis of breast cancer incidence and survival by subtype in Ontario women.

Background: Breast cancer (bca) is the type of cancer most frequently diagnosed among women in Canada. Breast cancer is categorized into various molecular subtypes by the expression of estrogen receptor (er), progesterone receptor (pgr), and her2 (human epidermal growth factor receptor 2). Currently, Canada has no national cancer registry with epidemiology data by subtype. Thus, we conducted a study to determine incidence, survival, and clinicopathologic characteristics by bca subtype [triple negative breast cancer (tnbc); her2+; and hormone receptor-positive (hr+), her2-] in Canadian women newly diagnosed with bca. Methods: Female patients diagnosed between 1 April 2012 and 31 March 2016 (fiscal 2012-2015) were identified in the Ontario Cancer Registry, and individual patient data were linked to data in provincial health administrative databases. Descriptive statistics and Kaplan-Meier curves were generated. Results: In this cohort, 3277 women (9.5%) had tnbc, 4902 (14.3%) had her2+ bca, and 22,247 (64.8%) had hr+, her2-breast cancer. The annual incidence was 15 per 100,000 for the tnbc group, 21-23 per 100,000 for the her2+ group, and 97-105 per 100,000 for the hr+, her2- group. The lowest median overall survival (mos) of 8.9 months was observed in women with clinical stage iv tnbc. In comparison, the mos was 37.3 months in those with her2+ disease and 35.2 months in those with and hr+, her2- metastatic bca. Conclusions: In the present study, the most recent and largest administrative database analysis of a Canadian population to date, we observed a subtype distribution consistent with previously reported data, together with comparable annual incidence and overall survival patterns.

Cost-of-illness study for non-small-cell lung cancer using real-world data.

Background: With recent advances in the treatment of non-small-cell lung cancer (nsclc) and current fiscal constraints within publicly funded health care systems, understanding the real-world economic effect of lung cancer management has become important. The objective of the present study was to determine the costs and resources used in the management of nsclc cohorts in Ontario. Methods: Patients diagnosed between 1 April 2010 and 31 March 2015 were identified in the Ontario Cancer Registry and linked to provincial administrative databases, capturing resources such as hospitalizations, cancer clinic visits, physician services, and systemic therapies or radiotherapy. A cost-of-illness analysis using a bottom-up approach and the GETCOST macro available at ices determined the overall total and mean costs in 2017 Canadian dollars. Resource utilization results were analyzed according to the total number of encounters per resource, the number of patients using each resource, and the number of encounters per patient. A separate cost-and-resource analysis was conducted for radiotherapy. Results: The 24,729 nsclc patients identified included 4542 with stage iii unresectable disease and 10,103 with stage iv nonsquamous disease. The overall total cost for all nsclc patients was $1.9 billion, with inpatient hospitalizations ($635.2 million), cancer clinic visits ($323.7 million), and physician services ($301.4 million) being the top cost contributors. The mean cost per patient was $76,816. The total cost of radiotherapy was $38.5 million. Conclusions: Real-world costs for the management of nsclc during the 5-year period examined were substantial, despite the fact that median survival was poor and treatment information was limited.

The generation of two specific cancer costing algorithms using Ontario administrative databases.

Cancer treatment and management have become increasingly economically burdensome. Consequently, to help with planning health service delivery, it is vital to understand the associated costs. Administrative databases can be used to help understand and generate real-world system-level costs. Using databases to generate costs can take one of two approaches: top-down or bottom-up. Top-down approaches disaggregate the total health care spending from a global health care budget by sector and provider. A bottom-up approach begins with individual-level health care use and its costs, which are then aggregated.

The cost of moderate and severe COPD exacerbations to the Canadian healthcare system.

BACKGROUND: The cost of exacerbations in chronic obstructive pulmonary disease (COPD) has not been well studied. The aim of this study was to identify and quantify the (average) cost of moderate and severe exacerbations (ME and SE, respectively) from a Canadian perspective. METHODS: Resources used during ME and SE were identified in a year long prospective, observational study (Resource Utilization Study In COPD (RUSIC)). The units of analysis were ME and SE. Unit costs (2006$CAN), based on provincial, hospital and published sources, were applied to resources. The overall cost per ME and SE were calculated. The population burden of exacerbations was also calculated. RESULTS: Among study participants (N=609, aged 68.6+/-9.4 years, 58.3% male) there were 790 exacerbations: 639 (80.9%) MEs and 151 (19.1%) SEs. Of the 790 exacerbations, 618 (78.2%), 245 (31.0%) and 151 (19.1%) included a visit to an outpatient clinic, emergency department (ED) or hospital, respectively. For ME, 85.9% and 13.1% involved visits to GPs and respirologists, respectively. Pharmacologic treatment changes in the outpatient setting involved antibiotics (63.1%) and corticosteroids (34.7%). The overall mean costs for outpatient and ED services for MEs were $126 (N=574) and $515 (N=105), respectively. The average overall cost of a ME was $641. For SEs, the average hospital stay was 10.0 days. The overall mean costs of outpatient, ED and hospitalization services for SE were $114 (N=44), $774 (N=140) and $8669 (N=151), respectively. The average overall cost of a SE was $9557. CONCLUSION: The economic burden associated with MEs and especially SEs, in Canada, is considerable and likely has a substantial impact on healthcare costs. The overall burden of exacerbations has been estimated in the range of $646 million to $736 million per annum.

Rash rates with egfr inhibitors: meta-analysis.

INTRODUCTION: Currently marketed epidermal growth factor receptor inhibitors (egfris) have been associated with high rates of dermatologic toxicity. METHODS: We formally reviewed the literature at medline and embase. Additional searches were conducted using Internet search engines. Studies were eligible if they were randomized controlled clinical trials of egfris, specifically cetuximab and panitumumab, in which at least one arm consisted of a non-egfri treatment and rash safety data were reported. The random effects method was used to pool differences in incident rash rates. Results are summarized as differences in incident rash (egfri therapy rate minus the non-egfri therapy rate) with corresponding 95% confidence intervals (cis) for all severity grades of rash and for grades 3 and 4 rash. RESULTS: Sixteen studies met the initial inclusion criteria of randomized controlled trials comparing egfri with non-egfri therapy. Seven publications that provided information on all severity grades of rash were found to have an overall difference in incident rash rate of 0.74 (95% ci: 0.68 to 0.81; p < 0.01). Thirteen studies that reported the incidence of grades 3 and 4 rash showed an overall difference in the incident rash rate of 0.12 (95% ci: 0.09 to 0.14; p < 0.01) between egfri and non-egfri therapy. Sensitivity analyses showed that the results were generally robust, but sensitive to small samples. CONCLUSIONS: Results quantify the difference in rash rates between egfri and non-egfri therapy.