Real-World Outcomes of Patients with Advanced Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer in Canada Using Data Extracted by Large Language Model-Based Artificial Intelligence.

Real-world evidence for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study's objective was to use previously validated DARWENTM artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe EGFR mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease. Of these, 136 (22%) had common sensitizing EGFR mutations (cEGFRm; ex19del, L858R), 8 (1%) had exon 20 insertions (ex20ins), and 338 (55%) had EGFR wild type. One-year overall survival (OS) (95% CI) for patients with cEGFRm, ex20ins, and EGFR wild type tumours was 88% (83, 94), 100% (100, 100), and 59% (53, 65), respectively. In total, 38% patients with ex20ins received experimental ex20ins targeting treatment as their first-line therapy. A total of 57 patients (36%) with cEGFRm received osimertinib as their first-line treatment, and 61 (39%) received it as their second-line treatment. One-year OS (95% CI) following the discontinuation of osimertinib was 35% (17, 75) post-first-line and 20% (9, 44) post-second-line. In this real-world AI-generated dataset, survival post-osimertinib was poor in patients with cEGFR mutations. Patients with ex20ins in this cohort had improved outcomes, possibly due to ex20ins targeting treatment, highlighting the need for more effective treatments for patients with advanced EGFRm NSCLC.

Estimating the Associated Burden of Illness and Healthcare Utilization of Newly Diagnosed Patients Aged ≥65 with Mantle Cell Lymphoma (MCL) in Ontario, Canada.

BACKGROUND: With the emergence of therapies for mantle cell lymphoma (MCL), understanding the treatment patterns and burden of illness among older patients with MCL in Canada is essential to inform decision making. METHODS: A retrospective study using administrative data matched individuals aged ≥65 who were newly diagnosed with MCL between 1 January 2013 and 31 December 2016 with general population controls. Cases were followed for up to 3 years in order to assess healthcare resource utilization (HCRU), healthcare costs, time to next treatment or death (TTNTD), and overall survival (OS); all were stratified according to first-line treatment. RESULTS: This study matched 159 MCL patients to 636 controls. Direct healthcare costs were highest among MCL patients in the first year following diagnosis (Y1: CAD 77,555 ± 40,789), decreased subsequently (Y2: CAD 40,093 ± 28,720; Y3: CAD 36,059 ± 36,303), and were consistently higher than the costs for controls. The 3-year OS after MCL diagnosis was 68.6%, with patients receiving bendamustine + rituximab (BR) experiencing a significantly higher OS compared to patients treated with other regimens (72.4% vs. 55.6%, p = 0.041). Approximately 40.9% of MCL patients initiated a second-line therapy or died within 3 years. CONCLUSION: Newly diagnosed MCL presents a substantial burden to the healthcare system, with almost half of all patients progressing to a second-line therapy or death within 3 years.

External Validation of the FLIPI Risk Score Measured at Diagnosis and POD24 Among Individuals With Follicular Lymphoma at the Time of Subsequent Relapse.

BACKGROUND: The Follicular lymphoma international prognostic index (FLIPI) risk score and POD24 have previously been shown to have prognostic value in follicular lymphoma (FL), but the extent to which they can inform prognosis at the time of subsequent relapse is uncertain. PATIENTS AND METHODS: We conducted a longitudinal cohort study of individuals diagnosed with FL between 2004 and 2010 in Alberta, Canada who received front-line therapy and subsequently relapsed. FLIPI covariates were measured prior to the initiation of front-line therapy. Median overall survival (OS), progression-free survival (PFS2), and time to next treatment (TTNT2) were estimated from the time of relapse. RESULTS: A total of 216 individuals were included. The FLIPI risk score was highly prognostic at the time of relapse for OS (c-statistic = 0.70; HR[High vs. Low] = 7.38; 95% CI: 3.05-17.88), PFS2 (c-statistic = 0.68; HR[High vs. Low] = 5.84; 95% CI: 2.93-11.62) and TTNT2 (c-statistic = 0.68; HR[High vs. Low] = 5.72; 95% CI: 2.87-11.41). POD24 was not prognostic at the time of relapse for either OS, PFS2, or TTNT2 (c-statistic = 0.55). CONCLUSION: The FLIPI score measured at diagnosis may help with the risk stratification of individuals with relapsed FL.

Estimating the Burden of Illness of Relapsed Follicular Lymphoma and Marginal Zone Lymphoma in Ontario, Canada.

BACKGROUND: Many patients with advanced follicular lymphoma (FL) and marginal zone lymphoma (MZL) relapse after first-line chemotherapy. OBJECTIVE: To examine healthcare resource utilization (HCRU) and cost, treatment patterns, progression, and survival of patients with FL and MZL who relapse after first-line treatment, in Ontario, Canada. METHODS: A retrospective, administrative data study identified patients with relapsed FL and MZL (1 January 2005-31 December 2018). Patients were followed for up to three years post relapse to assess HCRU, healthcare costs, time to next treatment (TTNT), and overall survival (OS), stratified by first- and second-line treatment. RESULTS: The study identified 285 FL and 68 MZL cases who relapsed after first-line treatment. Average duration of first-line treatment was 12.4 and 13.4 months for FL and MZL patients, respectively. Drug (35.9%) and cancer clinic costs (28.1%) were major contributors to higher costs in year 1. Three-year OS was 83.9% after FL and 74.2% after MZL relapse. No statistically significant differences were observed in TTNT and OS between patients with FL who received R-CHOP/R-CVP/BR in the first line only versus both the first- and second- line. A total of 31% of FL and 34% of MZL patients progressed to third-line treatment within three years of initial relapse. CONCLUSION: Relapsing and remitting nature of FL and MZL in a subset of patients results in substantial burden to patients and the healthcare system.

Prevalence, Treatment Patterns, and Outcomes of Individuals with EGFR Positive Metastatic Non-Small Cell Lung Cancer in a Canadian Real-World Setting: A Comparison of Exon 19 Deletion, L858R, and Exon 20 Insertion EGFR Mutation Carriers.

Real-world evidence surrounding EGFR positive NSCLC patients in Canada is limited. Administrative databases in Alberta, Canada were used to evaluate EGFR testing and mutation prevalence in de novo metastatic NSCLC, as well as the characteristics, treatment patterns, and outcomes of individuals with Exon 19, L858R and Exon20ins mutations. Between 2013-2019, 2974 individuals underwent EGFR testing, of which 451 (15.2%) were EGFR positive. Among EGFR positive individuals, 221 (49.0%) had an Exon 19 mutation, 159 (35.3%) had an L858R mutation, and 18 (4%) had an Exon20ins mutation. The proportion of individuals who initiated 1L systemic therapy was 89.1% for Exon19, 85.5% for L858R, and 72.2% for Exon20ins carriers. The primary front-line systemic therapy was gefitinib or afatinib monotherapy for individuals with Exon 19 (93.4%) and L858R (94.1%) mutations versus platinum combination therapy for individuals with Exon20ins mutations (61.5%). The Exon20ins cohort had worse median overall survival from initiation of 1L systemic therapy (10.5 months [95% CI: 8.0-not estimable]) than the Exon19 (20.6 months [95% CI: 18.4-24.9]), and L858R cohorts (19.1 months [95% CI: 14.5-23.1]). These findings highlight that Exon20ins mutations represent a rare subset of NSCLC in which treatment options are limited and survival outcomes are worse relative to individuals with more common types of EGFR mutations.

Intravenous Immunoglobulin (IVIg) Utilization in Immune Thrombocytopenia (ITP): A Multi-Center, Retrospective Review.

INTRODUCTION: Intravenous immunoglobulin (IVIg) is an immune thrombocytopenia (ITP) therapy, which is associated with toxicities, limited availability, increasing utilization, and high cost. This study aimed to assess short- and long-term IVIg utilization in patients with ITP at two tertiary care centers in Ontario, Canada, to determine the proportion of IVIg used in ITP compared with all usage, and to forecast IVIg demand in ITP. METHODS: Records from all adult ITP patients who received IVIg between January 1, 2003, and September 30, 2012, at Hamilton Health Sciences and London Health Sciences Centre were reviewed retrospectively. RESULTS: During the study period, 383 adult ITP patients (mean age 51.3 years) received a total of 2,098 IVIg infusions (London 547 infusions in 150 patients; Hamilton 1,551 infusions in 233 patients). ITP accounted for 5.6 and 9.1 % of all IVIg usage in London and Hamilton, respectively. The treatments included 264 (53.7 %) acute, 172 (35.0 %) short-term, and 56 (11.4 %) long-term treatments. The amounts of IVIg used for short- and long-term treatment of ITP are forecasted to be approximately 5,000 and 11,000 g per year, respectively, up to 2018. Together, these two centers represent 19.9 % of the provincial IVIg utilization. Assuming similar patient populations and practice patterns in Ontario, the overall provincial cost of IVIg use in ITP may be as high as $5 million annually. CONCLUSION: Short- and long-term IVIg utilization for ITP will remain an expensive resource within the Ontario provincial health care system. Physicians and policy makers should reflect on the impact of treating ITP with IVIg and should consider alternatives, where appropriate, to improve patient quality of life and decrease economic costs.

Prolonged progression-free survival and preserved quality of life in the Canadian prospective study of tositumomab and iodine(131)-tositumomab for previously treated, rituximab-exposed, indolent non-Hodgkin lymphoma.

Radioimmunotherapy offers a unique treatment modality for indolent non-Hodgkin lymphoma (iNHL). We report 5-year outcomes and quality of life (QoL) in tositumomab and iodine(131)-tositumomab (TST/I(131)-TST) treated patients with iNHL previously treated with rituximab. Ninety-three patients with ≥ 2 lines of therapy, responding to last treatment, were enrolled at 12 Canadian centers. Median age, disease duration and number of prior therapies (#PTx) were 59 years, 4.9 years and 5, respectively. Outcomes were response rate (43.0%), median progression-free survival (mPFS) (12.0 months), 5-year PFS (27%) and median overall survival (OS) (59.8 months). In responders, median response duration and mPFS were not reached. Improvements in QoL were seen by week 7. In univariate and multivariate analyses, hemoglobin, disease bulk and body surface area (BSA) predicted OS, whereas lactate dehydrogenase (LDH), bulk, BSA and #PTx predicted PFS. Most common adverse events (AEs) were fatigue and nausea. Two cases of myelodysplastic syndrome (MDS) were reported. TST/I(131)-TST was associated with durable responses, and prolonged OS and PFS in heavily pretreated iNHL.

Measuring treatment preferences and willingness to pay for docetaxel in advanced ovarian cancer.

BACKGROUND: Docetaxel is an equally active alternative to paclitaxel in advanced ovarian cancer but has a different adverse effect profile. Whilst paclitaxel is associated with less haematological toxicity, such as febrile neutropenia and anaemia, docetaxel causes less sensory and motor neuropathy. OBJECTIVE: To measure the economic value and preference scores for docetaxel as an alternative to paclitaxel in patients with advanced ovarian cancer. DESIGN AND SETTING: A cost-benefit analysis using a consumer-based willingness-to-pay (WTP) approach was conducted. The study population consisted of a patient surrogate sample comprised of 80 oncology pharmacists and nurses from eight Canadian provinces. Background information on ovarian cancer was provided including its current management, and differences in adverse effects between docetaxel and paclitaxel. Respondents were then asked what their preferred product would be if they were diagnosed with ovarian cancer and how much they would be willing to pay per cycle for six cycles in the form of a co-payment (i.e. user's fee) for the product of their choice. The maximum willingness to pay for docetaxel was then compared against the incremental cost (acquisition and administration) of the drug. STUDY PERSPECTIVE: Canadian healthcare system perspective. MAIN OUTCOME MEASURES AND RESULTS: The WTP survey instrument was simple to administer and easily understood by participants. Respondents ranked motor neuropathy as being the most unpleasant adverse effect of treatment. Of the sample, 63.8% preferred to use docetaxel instead of paclitaxel (p = 0.075). The patient surrogate sample was willing to pay a mean of 64 Canadian dollars (dollars Can; 2003 values) [95% CI dollars Can33, dollars Can92] per cycle for the benefits offered by docetaxel as an alternative to paclitaxel. This estimate was marginally lower than the incremental cost of dollars Can87 per cycle of docetaxel. CONCLUSION: A substantial portion of Canadian patients with ovarian cancer would likely prefer to be treated with docetaxel instead of paclitaxel for the management of their disease and would be willing to pay a portion of the incremental cost. Therefore, both options should be offered to patients, and selection of treatment can be based on reducing the risk of the toxicity that concerns the patient the most.