The projected health and economic impact of increased colorectal cancer screening participation among Canadians by income quintile.

OBJECTIVES: Disparities in colorectal cancer (CRC) screening uptake by socioeconomic status have been observed in Canada. We used the OncoSim-Colorectal model to evaluate the health and economic outcomes associated with increasing the participation rates of CRC screening programs to 60% among Canadians in different income quintiles. METHODS: Baseline CRC screening participation rates were obtained from the 2017 Canadian Community Health Survey. The survey participants were categorized into income quintiles using their reported household income and 2016 Canadian Census income quintile thresholds. Within each quintile, the participation rate was the proportion of respondents aged 50-74 who reported having had a fecal test in the past two years. Using the OncoSim-Colorectal model, we simulated an increase in CRC screening uptake to 60% across income quintiles to assess the effects on CRC incidence, mortality, and associated economic costs from 2024 to 2073. RESULTS: Increasing CRC screening participation rates to 60% across all income quintiles would prevent 69,100 CRC cases and 36,600 CRC deaths over 50 years. The improvement of clinical outcomes would also translate to increased person-years and health-adjusted person-years. The largest impact was observed in the lowest income group, with 22,200 cases and 11,700 deaths prevented over 50 years. Increased participation could lead to higher screening costs ($121 million CAD more per year) and lower treatments costs ($95 million CAD less per year), averaged over the period 2024-2073. CONCLUSION: Increased screening participation will improve clinical outcomes across all income groups while alleviating associated treatment costs. The benefits of increased participation will be strongest among the lowest income quintile.

RéSUMé: OBJECTIFS: Des disparités dans le recours au dépistage du cancer colorectal (CCR) selon le statut socioéconomique sont observées au Canada. Nous avons utilisé le modèle OncoSim-Colorectal pour évaluer les résultats cliniques et économiques associés à une augmentation à 60 % des taux de participation aux programmes de dépistage du CCR chez les Canadiennes et les Canadiens appartenant à différents quintiles de revenu. MéTHODE: Les taux de participation de référence au dépistage du CCR provenaient de l'Enquête sur la santé dans les collectivités canadiennes de 2017. Nous avons catégorisé les participantes et les participants de l'enquête en quintiles de revenu à l'aide du revenu du ménage déclaré et des seuils de quintiles de revenu du Recensement du Canada de 2016. Dans chaque quintile, le taux de participation était la proportion des répondantes et des répondants de 50 à 74 ans ayant dit avoir subi un test fécal au cours des deux années antérieures. À l'aide du modèle OncoSim-Colorectal, nous avons simulé une augmentation à 60 % du recours au dépistage du CCR dans tous les quintiles de revenu pour en évaluer les effets sur l'incidence, la mortalité et les coûts économiques associés du CCR entre 2024 et 2073. RéSULTATS: L'augmentation des taux de participation au dépistage du CCR à 60 % dans tous les quintiles de revenu préviendrait 69 100 cas de CCR et 36 600 décès dus au CCR sur 50 ans. L'amélioration des résultats cliniques se traduirait aussi par une augmentation des personnes-années et des personnes-années corrigées en fonction de la santé. Nous avons observé l'effet le plus marquant dans la catégorie de revenu inférieure, avec la prévention de 22 200 cas et de 11 700 décès sur 50 ans. La participation accrue pourrait entraîner une hausse des coûts de dépistage (121 millions de dollars canadiens de plus par année) et une baisse des coûts de traitement (95 millions de dollars canadiens de moins par année), en moyenne, sur la période de 2024 à 2073. CONCLUSION: La participation accrue au dépistage améliorera les résultats cliniques dans toutes les catégories de revenu tout en réduisant les coûts de traitement associés. Les avantages d'une participation accrue seront les plus marquants dans le quintile de revenu inférieur.

Adjuvant Ovarian Function Suppression in Premenopausal Hormone Receptor-Positive Breast Cancer.

Importance: Few oncology studies have assessed the effectiveness of adjuvant ovarian function suppression (OFS) in observational settings for premenopausal hormone receptor-positive breast cancer. Target trial emulation is increasingly used for estimating treatment outcomes in observational cohorts. Objectives: To describe hormone therapy and OFS treatment patterns (aim 1), examine the association between adding OFS to tamoxifen (TAM) or aromatase inhibitor (AI) and survival (aim 2), and examine the association between duration of hormone treatment (TAM or AI) plus OFS (H-OFS) and survival (aim 3). Design, Setting, and Participants: This population-based cohort study included all premenopausal, early-stage breast cancer diagnoses between 2010 and 2020 in Alberta, Canada. Target trial emulation was conducted. Eligibility criteria were directly modeled after the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT). Participants were followed up for a maximum of 5 years. Data were analyzed from July 2022 through March 2023. Exposures: For aim 2, exposures were receiving the following baseline treatments for 2 years: AI + OFS (AI-OFS), TAM + OFS (T-OFS), and TAM alone. For aim 3, exposures were a 2-year or greater and a less than 2-year duration of H-OFS. Main Outcomes and Measures: Recurrence-free survival was the primary outcome of interest. Marginal structural Cox models with inverse probability treatment and censoring weights were used to estimate hazard ratios (HRs), adjusted for baseline and time-varying confounding variables. Results: Among 3434 female patients with premenopausal, early-stage breast cancer diagnoses (median [IQR] age, 45 [40-48] years), 2647 individuals satisfied SOFT and TEXT eligibility criteria. There were 2260 patients who initiated TAM, 232 patients who initiated T-OFS, and 155 patients who initiated AI-OFS; 192 patients received H-OFS for 2 or more years, and 195 patients received H-OFS for less than 2 years. The 5-year recurrence risks were not significantly lower in AI-OFS vs TAM (HR, 0.76; 95% CI, 0.38-1.33) or T-OFS vs TAM (HR, 0.87; 95% CI, 0.50-1.45) groups. Patients receiving H-OFS for 2 or more years had significantly better 5-year recurrence-free survival compared with those receiving H-OFS for less than 2 years (HR, 0.69; 95% CI, 0.54-0.90). Conclusions and Relevance: This study found no significant reductions in recurrence risk for AI-OFS and T-OFS compared with TAM alone. H-OFS duration for at least 2 years was associated with significantly improved recurrence-free survival.

Text analysis framework for identifying mutations among non-small cell lung cancer patients from laboratory data.

BACKGROUND: Laboratory data can provide great value to support research aimed at reducing the incidence, prolonging survival and enhancing outcomes of cancer. Data is characterized by the information it carries and the format it holds. Data captured in Alberta's biomarker laboratory repository is free text, cluttered and rouge. Such data format limits its utility and prohibits broader adoption and research development. Text analysis for information extraction of unstructured data can change this and lead to more complete analyses. Previous work on extracting relevant information from free text, unstructured data employed Natural Language Processing (NLP), Machine Learning (ML), rule-based Information Extraction (IE) methods, or a hybrid combination between them. METHODS: In our study, text analysis was performed on Alberta Precision Laboratories data which consisted of 95,854 entries from the Southern Alberta Dataset (SAD) and 6944 entries from the Northern Alberta Dataset (NAD). The data covers all of Alberta and is completely population-based. Our proposed framework is built around rule-based IE methods. It incorporates topics such as Syntax and Lexical analyses to achieve deterministic extraction of data from biomarker laboratory data (i.e., Epidermal Growth Factor Receptor (EGFR) test results). Lexical analysis compromises of data cleaning and pre-processing, Rich Text Format text conversion into readable plain text format, and normalization and tokenization of text. The framework then passes the text into the Syntax analysis stage which includes the rule-based method of extracting relevant data. Rule-based patterns of the test result are identified, and a Context Free Grammar then generates the rules of information extraction. Finally, the results are linked with the Alberta Cancer Registry to support real-world cancer research studies. RESULTS: Of the original 5512 entries in the SAD dataset and 5017 entries in the NAD dataset which were filtered for EGFR, the framework yielded 5129 and 3388 extracted EGFR test results from the SAD and NAD datasets, respectively. An accuracy of 97.5% was achieved on a random sample of 362 tests. CONCLUSIONS: We presented a text analysis framework to extract specific information from unstructured clinical data. Our proposed framework has shown that it can successfully extract relevant information from EGFR test results.

Real-world evaluation of access-driven Canadian treatment sequences in progressive prostate cancer (REACTIVATE).

INTRODUCTION: The results of the phase 3 ALSYMPCA trial showed that Radium-223 (Ra-223) improves overall survival (OS) and delays onset of first symptomatic skeletal event vs. placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of the REACTIVATE study was to inform the optimal placement of Ra-233 in the treatment sequence by evaluating clinical outcomes and healthcare resource utilization using real-world data from multiple Canadian provinces. METHODS: This retrospective cohort study analyzed patient outcomes according to Ra-223 placement using administrative databases of four Canadian provinces, encompassing 4301 patients with mCRPC who received at least two lines of life-prolonging therapy (LPT) for mCRPC. Outcomes included OS, event-free survival (EFS), and healthcare resource utilization. Each province was analyzed separately. RESULTS: OS, measured from the start of second-line LPT, differed between provinces: those in Ontario receiving second-line Ra-223 had a longer OS vs. those receiving it in third-line or later (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.66-0.95). There was no difference between lines of therapy in patients in British Columbia (HR 1.165, 95% CI, 0.894-1.518, p=0.2576), and OS was numerically worse but not statistically significant in patients receiving Ra-223 in second-line in Quebec (HR 1.44, 95% CI, 0.93-2.24). Other outcomes also varied across provinces, with second-line use of Ra-223 being associated with longer EFS and reduced healthcare utilization vs. third-line use in Ontario but not in Quebec. CONCLUSIONS: Significant heterogeneity exists in the management and outcomes of mCRPC between provinces, particularly regarding the placement of Ra-223 in the treatment sequence.

Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: A Double-Blind Randomized Controlled Trial.

PURPOSE: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS. METHODS: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression. RESULTS: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4). CONCLUSION: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

Treatment Patterns and Health Outcomes among Patients with HER2 IHC0/-Low Metastatic or Recurrent Breast Cancer.

Improved understanding of the biological heterogeneity of breast cancer (BC) has facilitated the development of more effective and personalized approaches to treatment. This study describes real-world evidence on treatment patterns and outcomes for a population-based cohort of patients with human epidermal growth factor receptor (HER2) IHC0 and -low BC with de novo or recurrent disease from Alberta, Canada. Patients 18+ years old diagnosed with HER2 IHC0/-low, de novo/recurrent BC from 2010 to 2019 were identified using Alberta's cancer registry. Analyses of these patients' existing electronic medical records and administrative claims data were conducted to examine patient characteristics, treatment patterns, and survival outcomes. A total of 3413 patients were included in the study, of which 72.10% initiated first line hormonal and non-hormonal systemic therapy. The 1-year overall survival (OS) was 81.09% [95% CI, 79.52-82.69]. Recurrent patients had a higher OS compared to de novo patients: 54.30 months [95% CI, 47.80-61.90] vs. 31.5 months [95% CI, 28.40-35.90], respectively. Median OS was 43.4 months [95% CI, 40.70-47.10] and 35.80 months [95% CI, 29.00-41.70] among patients with HER2-low and HER2 IHC0 cancer, respectively. The study results provide real-world evidence regarding the clinical outcomes of HER2 IHC0/-low and de novo/recurrent disease.

Real-World Treatment Patterns, Clinical Outcomes, and Healthcare Resource Utilization in Early-Stage Non-Small-Cell Lung Cancer.

The prognosis of early non-small-cell lung cancer (eNSCLC) remains poor. An understanding of current therapies and outcomes can provide insights into how novel therapies can be integrated into clinics. We conducted a large, retrospective, population-based cohort study of patients with de novo eNSCLC (stages IB, IIA, IIB, and IIIA) diagnosed in Alberta, Canada, between 2010 and 2019. The primary objectives were to describe treatment patterns and survival outcomes among patients with eNSCLC. A total of 5126 patients with eNSCLC were included. A total of 45.3% of patients were referred to a medical oncologist, ranging from 23.7% in stage IB to 58.3% in IIIA. A total of 23.6% of patients initiated systemic therapy (ST), ranging from 3.5% in stage IB to 38.5% in IIIA. For stage IIB and IIIA individuals who received surgery, adjuvant ST was associated with a decreased likelihood of death (hazard ratios (HR) of 0.77 (95% CI: 0.56-1.07) and 0.69 (95% CI: 0.54-0.89), respectively). In a Canadian real-world setting, stage IIB and IIIA patients who received adjuvant ST tended to have better survival than patients who did not, but future studies that provide adjustment of additional confounders are warranted. Examining referral pathways that account for disparities based on age, sex, and comorbidities in the real world would also provide further insights.

Real-World Safety and Effectiveness of a Bevacizumab Biosimilar (ABP 215) in Metastatic Colorectal Cancer Patients in Canada.

BACKGROUND: ABP 215 is a biosimilar to the reference product, bevacizumab, and was one of the first biosimilars approved by Health Canada for the first-line treatment of metastatic colorectal cancer (mCRC). This study aimed to address gaps in real-world evidence (RWE) including patient characteristics, treatment safety (primary objective), and effectiveness (secondary objective) for first-line ABP 215 therapy in Canadian patients with mCRC. MATERIALS AND METHODS: Retrospective data were collected in 2 waves, at least 1 year (Wave 1) or 2 years (Wave 2) after commercial availability of ABP 215 at each participating site. RESULTS: A total of 75 patients from Wave 1 and 164 patients from Wave 2 treated with a minimum of 1 cycle of ABP 215 were included. At least one safety event of interest (EOI) was recorded for 34.7% of Wave 1 and 42.7% of Wave 2 patients. The median progression free survival (PFS) for Wave 1 and 2 patients were 9.47 (95% confidence interval [CI]: 6.71, 11.90) and 21.38 (95% CI: 15.82, not estimable) months, respectively. Median overall survival was not estimable for Wave 1 and was 26.45 months for Wave 2. CONCLUSION: The safety and effectiveness of ABP 215 observed in this real-world study were comparable to clinical trial findings and to other RWE with longer PFS in the current study.

Association between treatment and improvements in overall survival of patients with advanced/metastatic non-small cell lung cancer since 2011: A study in the United States, Canada, and Germany using retrospective real-world databases.

BACKGROUND: This study aimed to describe treatment patterns and overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) in three countries between 2011 and 2020. METHODS: Three databases (US, Canada, Germany) were used to identify incident aNSCLC patients. OS was assessed from the date of incident aNSCLC diagnosis and, for patients who received at least a first line of therapy (1LOT), from the date of 1LOT initiation. In multivariable analyses, we analyzed the influence of index year and type of prescribed treatment on OS. FINDINGS: We included 51,318 patients with an incident aNSCLC diagnosis. The percentage of patients treated with a 1LOT differed substantially between countries, whereas the number of patients receiving immunotherapies/targeted treatments increased over time in all three countries. Median OS from the date of incident diagnosis was 9.9 months in the United States vs. 4.1 months in Canada. When measured from the start of 1LOT, patients had a median OS of 10.7 months in the United States, 10.9 months in Canada, and 10.9 months in Germany. OS from the start of 1LOT improved in all three countries from 2011 to 2020 by approximately 3 to 4 months. CONCLUSIONS: Observed continuous improvement in OS among patients receiving at least a 1LOT from 2011 to 2020 was likely driven by improved care and changes in the treatment landscape. The difference in the proportion of patients receiving a 1LOT in the observed countries requires further investigation.

Adjuvant Systemic Therapies for Resected Stages III and IV Melanoma: A Multi-Center Retrospective Clinical Study.

BACKGROUND: Adjuvant therapies have been approved for resected melanoma based on improved recurrence-free survival. We present early findings from a real-world study on adjuvant treatments for melanoma. METHODS: A comprehensive chart review was conducted for patients receiving adjuvant systemic therapy for resected high-risk stages III and IV melanoma. Statistical analysis was performed to assess recurrence-free survival and subgroup differences. RESULTS: A total of 149 patients (median age = 58.0 years, 61.1% men, 49.7% with BRAF V600E/K genotypes) were included, with 94.6% having resected stage III melanoma. Anti-PD-1 immunotherapy was received by 86.5% of patients, while 13.4% received BRAF-targeted therapy. At a median follow-up of 22.4 months, the recurrence rate was 31.5%, with 1-year and 2-year recurrence-free survival rates of 79% and 62%, respectively. Similar recurrence rates were observed between anti-PD-1 immunotherapy and BRAF-targeted therapy. Long-term toxicity affected 27.4% of patients, with endocrinopathies and late-emergent immune-related adverse events being common. CONCLUSIONS: Real-world adjuvant systemic therapy aligns with clinical trial practice. Recurrence rates remain high despite treatment, and long-term toxicities, including endocrinopathies and chronic inflammatory conditions, are not uncommon.

The Impact of BRAF Mutation Status on Survival Outcomes and Treatment Patterns among Metastatic Colorectal Cancer Patients in Alberta, Canada.

Colorectal cancer presents via multiple different clinical phenotypes that can arise from a variety of different genetic and molecular alterations. The aim of this study was to describe survival outcomes and treatment patterns of metastatic colorectal cancer (mCRC) patients by v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation status. The Alberta Cancer Registry was used to identify all patients >18 years old who had been diagnosed with mCRC in Alberta between 1 January 2017 and 31 December 2019 and had received at least one cycle of systemic therapy. Treatment patterns were compared between wild-type and mutant BRAF mCRC patients. Cox regression models and Kaplan-Meier curves were created to assess survival differences by both treatment pattern and BRAF status. A total of 488 patients were identified with mCRC, of which 42 (11.4%) were confirmed to have a BRAF mutation. The most common first-line treatment regimen was either capecitabine and oxaliplatin (CAPOX) or leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX). The median overall survival for mCRC patients was 20.01 months. Mutant BRAF patients had a median survival of 8.21 months compared to 20.03 months among those with wild-type BRAF. BRAF mutations among mCRC patients are associated with a considerably poor prognosis, reinforcing the need for clinical BRAF testing among newly diagnosed patients to better understand their prognosis.

Data collection within patient support programs in Canada and implications for real-world evidence generation: the authors' perspective.

Patient support programs (PSPs) offer a unique opportunity to collect real-world data that can contribute to improving patient care and informing healthcare decision making. In this perspective article, we explore the collection of data through PSPs in Canada, current advances in data collection methods, and the potential for generating acceptable real-world evidence (RWE). With PSP infrastructure already in place for most specialized drugs in Canada, adding and strengthening data collection capacities has been a focus in recent years. However, limitations in PSP data, including challenges related to quality, bias, and trust, need to be acknowledged and addressed. Forward-thinking PSP developers have been taking steps to strengthen the PSP datasphere, such as engaging third parties for data analysis, publishing peer-reviewed studies that utilize PSPs as a data source and incorporating quality controls into data collection processes. This article illustrates the current state of PSP data collection by examining six PSP RWE studies and outlining their data characteristics and the health outcomes collected from the PSP. A framework for collecting real-world data within a PSP and a checklist to address issues of trust and bias in PSP data collection is also provided. Collaboration between drug manufacturers, PSP vendors, and data specialists will be crucial in elevating PSP data to a level acceptable to healthcare decision makers, including health technology assessors and payers, with the ultimate beneficiary being patients.

Effectiveness of Immune Checkpoint Inhibitor with Anti-PD-1 Monotherapy or in Combination with Ipilimumab in Younger versus Older Adults with Advanced Melanoma.

Background: The majority of melanoma is diagnosed in individuals between 55 and 84 years old. Current data varied in reporting differences in survival outcomes amongst different age groups. Methods: A retrospective, multi-center, provincial cohort database was used to investigate the relationship between age (<65 or ≥65 years old) and overall survival. Patients must have had histologically confirmed locally advanced or metastatic melanoma and had to have received at least one cycle of immunotherapy (single agent nivolumab, pembrolizumab, or combination ipilimumab plus nivolumab). Results: From August 2013 to May 2020, we identified 497 patients (median age = 64 [range 12-96 years]; 65.2% men; 36.4% with a BRAF mutation (V600E and V600K)). Of these, 260 were < 65 years old, and 237 were ≥65 years old. A total of 39.1% of the patients in the younger cohort received combination ICI compared with 10.2% in the older cohort, and the difference was statistically significant. Median survival amongst individuals aged ≥65 years old was shorter compared to individuals <65 years old, with a median overall survival of 17.1 (95% CI 12.3-22.9 months) months and 22.2 months (95% CI 18.7-33.8 months), respectively (p = 0.04), at a median follow-up of 34.4 months (range: 1.84-81.4 months). The survival difference was present in the cutaneous melanoma cohort where median OS was 18.2 months (95% CI 12.3-30.4 months) in patients ≥65 years old and 23.8 months (95% CI 19.2-48.2 months) in patients <65 years old, p = 0.04. There were no significant differences by age in the non-cutaneous melanoma cohort. A combination of nivolumab plus ipilimumab was associated with an improved overall survival hazard ratio of 0.48 (95% CI 0.36-0.65) as compared to anti-PD-1 monotherapy alone (p < 0.001). In the cutaneous cohort treated with anti-PD-1 monotherapy (n = 306), no significant differences were seen with median OS at 16.1 months (95% CI 11.4-25.7 months) in patients ≥65 years old and 17.1 months (95% CI 12.0-22.2 months) in patients <65 years old (p = 0.84). Tumor response to anti-PD-1 was higher in the older patients compared with the response in younger patients with cutaneous melanoma. Conclusions: Older melanoma patients have similar survival compared with younger patients after receiving the same treatment with anti-PD-1 monotherapy. The superior survival observed in the younger patients is possibly related to the higher utilization of combination ICI. Tumor response to immunotherapy is superior in older patients with cutaneous melanoma; however, younger patients may improve their survival by using combination ICI.

Comparative Effectiveness of Lurbinectedin for the Treatment of Relapsed Small Cell Lung Cancer in the Post-Platinum Setting: A Real-World Canadian Synthetic Control Arm Analysis.

BACKGROUND: Based on findings from a single-arm, phase 2 basket trial (NCT02454972), lurbinectedin may be an effective treatment for individuals with small cell lung cancer (SCLC) who progressed on or after platinum-based chemotherapy. OBJECTIVE: To estimate the comparative effectiveness of lurbinectedin versus the historical standard of care for relapsed SCLC in Canada. METHODS: A synthetic control arm (SCA) analysis was conducted using real-world data. Population-level data were obtained from real-world databases in Alberta, Canada. Individuals diagnosed with SCLC who initiated post-platinum systemic therapy and met approximated eligibility criteria from the lurbinectedin trial were included in the SCA. Median overall survival (OS) in the SCA was estimated after adjusting for chemotherapy-free interval (CTFI; < 90 versus ≥ 90 days) and stage at initial diagnosis (extensive versus limited). The CTFI-adjusted hazard ratio was estimated using a Cox proportional hazards model. RESULTS: One hundred seventy-four individuals were included in the SCA and 105 in the lurbinectedin trial. The adjusted median OS in the SCA was 6.1 months (95% CI 5.4-7.7 months; unadjusted: 6.7 months, 95% CI 6.0-7.7 months) versus 9.3 months (95% CI 6.3-11.8 months) in the lurbinectedin trial. The adjusted hazard ratio comparing lurbinectedin with the historical standard of care (referent group) was 0.61 (95% CI 0.45-0.82; unadjusted HR: 0.72; 95% CI 0.54-0.97). The hazard ratio was more pronounced among individuals with CTFI ≥ 90 days (HR: 0.49, 95% CI 0.33-0.73). CONCLUSION: These findings suggest improved OS with lurbinectedin monotherapy versus the historical standard of care in Alberta, Canada.

Decitabine/Cedazuridine in the Management of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia in Canada.

The management of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) is limited and remains an unmet need. Decitabine/cedazuridine (DEC-C, ASTX727) is Canada's first and only approved oral hypomethylating agent for MDS and CMML. We characterized the real-world use of DEC-C through a Canadian compassionate use program. Demographic and clinical data from 769 patients enrolled in Taiho Pharma Canada's Patient Support Program were collected and analyzed. These patients represent a collection period from 10 November 2020 to 31 August 2022 with a median age of 76 years. Among 651 patients who started DEC-C, the median treatment duration was 4.2 cycles. The median overall and progression-free survival were 21.6 and 10.7 months, respectively. Among 427 patients who discontinued treatment, the majority (69.5%) stopped due to death (n = 164) or disease progression (n = 133). Multivariable cox regression showed that age, province of residence, blast counts, antibiotic prophylaxis, and number of dose reductions and delays were not significantly associated with overall and progression-free survival. DEC-C is a promising alternative to parenteral hypomethylating agent therapy, and it likely addresses an important unmet need for effective and convenient therapies in this setting.

A Real-World Evidence Study Using Alberta-Population-Based Data to Describe Treatment Patterns for Metastatic Castration-Sensitive Prostate Cancer Patients (AWARENESS).

INTRODUCTION: Over the past decade, the treatment of metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly. Current guidelines suggest the use of androgen deprivation therapy (ADT) plus an additional systemic therapy, regardless of disease burden and risk, based on phase 1 evidence showing improved overall survival. We sought to describe treatment patterns of patients with mCSPC in the province of Alberta. METHODS: This was a retrospective, population-based, cohort study of male patients aged ≥18 with mCSPC at the time of diagnosis and who initiated ADT between 1 January 2016 and 31 December 2020. Data were obtained from the Alberta Cancer Registry. Patients were assigned to an ADT-alone cohort or a treatment intensification cohort (cohorts 2-5). The primary objectives of this study were to describe baseline characteristics and the treatment of mCSPC patients who initiated ADT with or without treatment intensification. Overall survival between cohorts was a secondary objective. Descriptive statistics were used to describe differences in baseline characteristics of each cohort. Overall survival was calculated using the Kaplan-Meier method. All statistical tests were two-sided and are used to call out likely cohort differences descriptively. RESULTS: Between 1 January 2016 and 31 December 2020, we identified a total of 960 patients with mCSPC (median age 74 years, IQR 66-82). Most patients received ADT alone (67%), followed by ADT plus abiraterone (18%), ADT plus docetaxel (12%), and ADT plus enzalutamide or apalutamide (3%). Over the study period, we observed an increase in the utilization of treatment intensification over time, in particular, the increased use of androgen-receptor-axis-targeted (ARAT) therapies. Patients who received ADT alone were older, were more likely to have more than one comorbid condition, had fewer sites of metastatic disease, and were less likely to be on opioid medications. CONCLUSIONS: In this study, we show that patients who received ADT alone as treatment for mCSPC are older, have more comorbidities, and have less extensive disease. While there has been a decline over time in the number of patients treated with ADT alone, over 50% of all patients with mCSPC continue to receive ADT alone. Further work is needed to understand barriers to treatment intensification and for knowledge translation initiatives to improve the treatment of patients with mCSPC.

Real-World Study to Assess Patterns of Treatment Practices and Clinical Outcomes in Metastatic Colorectal Cancer Patients with RAS Wild-Type Left-Sided Tumours in Canada.

Minimal Canadian data are available on the RAS testing rates, treatment patterns, and corresponding overall survival (OS) in metastatic colorectal cancer (mCRC) patients. We conducted a population-based cohort study of left-sided RAS wild-type (WT) mCRC patients diagnosed between 1 January 2014 and 31 December 2019, and who were treated with first-line (1L) chemotherapy plus the epidermal growth factor receptor inhibitor panitumumab, chemotherapy plus bevacizumab, or chemotherapy alone, in Alberta, Canada, using electronic medical records and administrative health system data. Of the 2721 patients identified with left-sided mCRC, 320 patients with RAS WT mCRC were treated with 1L systemic therapy: chemotherapy plus panitumumab (n = 64), chemotherapy plus bevacizumab (n = 52), or chemotherapy alone (n = 204). Only 65% and 39% of the 320 1L-treated patients initiated second- and third-line therapy, respectively. A total of 71% of individuals with treated left-sided mCRC underwent RAS testing. The median OS for mCRC patients with RAS WT left-sided tumours was higher for patients treated with 1L panitumumab plus chemotherapy (34.3 months; 95% CI: 23.8-39.6) than for patients who received 1L chemotherapy alone (30.0 months; 95% CI: 24.9-34.1) or 1L bevacizumab plus chemotherapy (25.6 months; 95% CI: 21.2-35.7). These findings highlight an unmet need in left-sided RAS WT mCRC, with relatively few individuals receiving a biologic agent in combination with chemotherapy in the 1L setting, a high rate of attrition between lines, and a need for increased RAS testing before treatment initiation.

Improving the efficiency of clinical trials in multiple sclerosis.

BACKGROUND: Phase 3 clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilized a limited number of conventional designs with a high degree of success. However, these designs limit the types of questions that can be addressed, and the time and cost required. Moreover, trials involving people with progressive multiple sclerosis (MS) have been less successful. OBJECTIVE: The objective of this paper is to discuss complex innovative trial designs, intermediate and composite outcomes and to improve the efficiency of trial design in MS and broaden questions that can be addressed, particularly as applied to progressive MS. METHODS: We held an international workshop with experts in clinical trial design. RESULTS: Recommendations include increasing the use of complex innovative designs, developing biomarkers to enrich progressive MS trial populations, prioritize intermediate outcomes for further development that target therapeutic mechanisms of action other than peripherally mediated inflammation, investigate acceptability to people with MS of data linkage for studying long-term outcomes of clinical trials, use Bayesian designs to potentially reduce sample sizes required for pediatric trials, and provide sustained funding for platform trials and registries that can support pragmatic trials. CONCLUSION: Novel trial designs and further development of intermediate outcomes may improve clinical trial efficiency in MS and address novel therapeutic questions.

Cost-Effectiveness of Surveillance after Metastasectomy of Stage IV Colorectal Cancer.

Surveillance of stage IV colorectal cancer (CRC) after curative-intent metastasectomy can be effective for detecting asymptomatic recurrence. Guidelines for various forms of surveillance exist but are supported by limited evidence. We aimed to determine the most cost-effective strategy for surveillance following curative-intent metastasectomy of stage IV CRC. We performed a decision analysis to compare four active surveillance strategies involving clinic visits and investigations elicited from National Comprehensive Cancer Network (NCCN) recommendations. Markov model inputs included data from a population-based cohort and literature-derived costs, utilities, and probabilities. The primary outcomes were costs (2021 Canadian dollars) and quality-adjusted life years (QALYs) gained. Over a 10-year base-case time horizon, surveillance with follow-ups every 12 months for 5 years was most economically favourable at a willingness-to-pay threshold of CAD 50,000 per QALY. These patterns were generally robust in the sensitivity analysis. A more intensive surveillance strategy was only favourable with a much higher willingness-to-pay threshold of approximately CAD 425,000 per QALY, with follow-ups every 3 months for 2 years then every 12 months for 3 additional years. Our findings are consistent with NCCN guidelines and justify the need for additional research to determine the impact of surveillance on CRC outcomes.

Real-world impact of patient-reported outcome measurement on overall survival, healthcare use and treatment discontinuation in cancer patients.

Aim: The purpose of this retrospective, population-based, observational cohort analysis was to assess whether routine patient-reported outcomes (PRO) monitoring alone has an impact on real-world overall survival (OS) and hospitalizations among individuals diagnosed with lung, breast or colorectal cancer. The importance of follow-up care in post-PRO data collection was also discussed. Patients & methods: Administrative databases covering 17 cancer centers from Alberta, Canada were queried and individuals ≥18 years old and diagnosed with lung, breast or colorectal cancer from 1 January 2016 to 31 December 2019 were included and followed until 31 December 2020. Patients were stratified by whether they received routine PRO monitoring initiated within 120 days of diagnosis and matched 1:1 with use of propensity scores based on baseline characteristics. OS was assessed from the index date to death, and the respective Kaplan-Meier curves were estimated along with hazard ratios from Cox Proportional Hazard Models. Linear and logistic regression models were used to estimate mean differences and odds ratios (OR) respectively for healthcare resource utilization events including cancer physician visits, emergency department visits and outpatient ambulatory care encounters. Results: 4800 patients were included in each matched cohort. There was no statistically significant difference between PRO monitoring and non-monitoring cohorts in OS (HR = 1.01; 95% CI: 0.93-1.09; p = 0.836) and treatment discontinuation (OR = 0.98; 95% CI: 0.85-1.12; p = 0.75). Median OS was 51.5 months for unmonitored cohort (95% CI: 47.5-NA) versus 50.6 months for monitored cohort (95% CI: 47.6-55.7). Compared with PRO-monitored patients, unmonitored patients were associated with lower hospitalization risks (OR = 1.12; 95% CI: 1.03-1.22; p = 0.01). However, PRO-monitored patients experienced significantly fewer physician visits in comparison to unmonitored patients (MD = -1.036; 95% CI: -1.288 to -0.784, p < 0.001). Conclusion: Our results show that capturing patient-reported symptoms alone reduced the number of physician visits but neither reduced hospitalizations nor improved OS in this real-world cancer population. To drive more meaningful clinical impact, PRO monitoring programs must be met with rigorous follow-up response to the identified symptoms.