Filter
Year(s):
Author(s):
Oral human papillomavirus (HPV) infection is a risk for oropharyngeal cancer (OPC), now the leading HPV-related cancer in males in Canada. P16 positivity is a marker of HPV positivity. Since 2015, all major Canadian cancer centers perform routine p16 tumor marker testing of OPCs to define their HPV status but recent data on the HPV-attributable fraction for OPC in Canada do not exist. A retrospective chart review was conducted of all squamous cell OPC cases in patients 18 years and older diagnosed from 2016 to 2020 in 4 major Canadian hospital-based regional oncology centers to determine the HPV attributable fraction for OPC in Canada using p16 as a surrogate marker for HPV. 1154 OPC cases were identified. Most patients (85.4%) were male; about one-third 26 (31.4%) had never smoked. Most OPC (80.6%) were P16 positive. p16 positivity was 27 associated with younger age (mean age p16+ 61.6 vs. p16- 66.5 years, p < 0.0001), male sex 28 (p16+ males 84.0% vs p16+ females 60.9%, p < 0.0001), lower tumor stage (Stage 1 p16+ 29 88.1% vs Stage 4 p16+ 69.4%, p < 0.001), and non-smoking (never smoked 92.3% vs past 30 smoker 82.8% vs current smoker 65.0%, p < 0.001). Logistic regression confirmed these 31 associations. This study, the largest cohort of Canadian patients with OPC yet reported, demonstrates the high attributable fraction for HPV-related OPC. HPV-related OPC was more likely in men, younger individuals, and never smokers. These findings highlight the burden of HPV-related OPC in Canada and support gender-neutral HPV vaccination as an important public health strategy to prevent head and neck cancer.
INTRODUCTION: There have been minimal advances in the systemic treatment of limited stage small cell lung cancer (LS-SCLC) for decades. With the publication of the ADRIATIC trial, consolidation durvalumab is a new standard of care. This study evaluated real-world treatments and clinical outcomes prior to the era of immunotherapy for LS-SCLC. METHODS: The Canadian Small Cell Lung Cancer Database (CASCADE) is a Canadian multi-institutional federated database that includes patients with SCLC from 9 academic institutions. This analysis included patients with pathologically confirmed LS-SCLC treated curatively between January 2001 and December 2022. Baseline characteristics and treatment patterns were obtained from medical records and assessed descriptively. The primary outcome was overall survival (OS) assessed using Kaplan Meier (KM) methods. OS was also assessed among patients who received treatment eligible for participation in the ADRIATIC trial. RESULTS: A total of 1,024 patients were included. Median age was 66 years old and 52 % of patients were female. Concurrent chemoradiation therapy (cCRT) was the most common treatment modality (76 %), followed by surgery (11 %) and sequential CRT (10 %). Median OS was 24.9 months (95 % confidence interval [CI] = 23.4-27.4). Only 36 % of patients treated with cCRT received treatment meeting eligibility criteria for the ADRIATIC trial. The most common reason for ineligibility was due to the radiation therapy (RT) dose/schedule used. Median OS of eligible and ineligible patients was 30.3 months (95 % CI = 26.4-36.4) versus 21.7 months (95 % CI = 19.7-24.9). CONCLUSIONS: Survival outcomes for LS-SCLC remain poor despite curative-intent multimodality treatment. Immunotherapy represents a promising advance but a high proportion of patients in the real-world receive treatment that was not represented in the ADRIATIC trial. Future work evaluating the outcomes of patients treated with immunotherapy is critical to assess its real-world impact.
Real-world studies have become more common in clinical literature in recent years, but many clinicians remain unfamiliar with real-world study design and statistical approaches. This vodcast intends to be a practical guide for clinicians by clarifying aspects of real-world study methodology. As both practicing oncologists and researchers with extensive real-world data experience, the hosts discuss types of study designs and real-world data source considerations. An overview of statistical techniques for mitigating treatment-selection bias is also provided, including propensity score matching, inverse probability of treatment weighting, and multivariable analysis. By combining high-quality data sources, careful sample size considerations, and rigorous statistical techniques, real-world studies can offer valuable insights into therapeutic effectiveness in routine clinical practice that supplement learnings from randomized clinical trials. This vodcast is designed to equip clinicians with the knowledge to critically evaluate real-world evidence and potentially apply it to their practice.Vodcast and infographic available for this article. Vodcast (MP4 1207725 KB) INFOGRAPHIC.
BACKGROUND AND OBJECTIVE: While the benefit of cabozantinib in metastatic renal cell carcinoma (mRCC) is well established post-tyrosine kinase inhibitor therapy, its comparative effectiveness versus sunitinib after first-line (1L) nivolumab-ipilimumab is uncertain. METHODS: A target trial emulation was designed using data from the IMDC to estimate the effect of second-line (2L) cabozantinib versus sunitinib within 18 months of discontinuing 1L nivolumab-ipilimumab on overall survival (OS). Patients diagnosed after January 1, 2017 were followed from initiation of 2L until death or last known contact. Inverse-probability of treatment weighting was used to adjust for hemoglobin, calcium, platelets, and neutrophils at 2L, Karnofsky performance score (KPS) at 2L, time from diagnosis to initiation of 2L, and response to 1L nivolumab-ipilimumab. Treatments were compared using adjusted Kaplan-Meier curves and adjusted hazard ratios (HR) from a Cox regression model. Missing data were addressed with multiple imputation by chained equations. E-values were used to assess the likelihood findings could be explained by residual confounding. KEY FINDINGS AND LIMITATIONS: A total of 120 and 121 patients who received cabozantinib or sunitinib after 1L nivolumab-ipilimumab were included. The proportion with a KPS < 80% at 2L (21% vs. 46% P = .001) and the overall response rate to first line therapy (12.7% vs. 17.9% P = .002) differed significantly between cabozantinib and sunitinib. The objective response was 27% for cabozantinib versus 20% for sunitinib with a median time to treatment failure of 8.5 (95% CI: 6.9-12.9) and 4.5 (95% CI: 3.7-5.8) months. Median OS was 21.4 (95% CI: 17.9-NA) months from initiation of cabozantinib and 10.1 (95% CI: 7.6-17.7) months for sunitinib (Adjusted HR 0.44 (95% CI: 0.22-0.86)). The E-value was 2.92, suggesting a low likelihood of findings being due to residual confounding alone. CONCLUSIONS: These data provide real-world evidence supporting cabozantinib as a second-line treatment option in mRCC following 1L nivolumab-ipilimumab.
BACKGROUND: Breast cancer is the most prevalent cancer and second leading cause of cancer-related mortality among Canadian women. Most of cases belong to the HR+/HER2- subtype, representing approximately two-thirds of all instances. OBJECTIVES: This real-world evidence study aims to comprehensively analyze the treatment pattern, and clinical outcomes of Canadian patients diagnosed with early-stage HR+/HER2- breast cancer. DESIGN: This retrospective, longitudinal cohort study involved 541 patients enrolled in the pan-Canadian cancer patient registry PMT (Personalize My Treatment). METHODS: The cohort included patients with newly diagnosed or recurrent stage II or III HR+/HER2- breast cancer between January 1st, 1992, and May 31st, 2022. Summary statistic to describe treatment pattern and Kaplan Meir analysis for clinical outcome were used. RESULTS: In the adjuvant setting, our study found that ET was administered to 75.6% of the cohort, with a significant preference for combining ET with cytotoxic agents and, particularly in stage III patients. In addition, neoadjuvant therapy, primarily using cytotoxic agents, was higher in stage III patients, and those receiving neoadjuvant therapy were more likely to either continue with ET as adjuvant treatment. The median duration of adjuvant ET was 4.5 years. In the adjuvant patient population, recurrence rates progressively increased over time from 13.2% after 2 years, 21.4% after 3 years, 30.3% after 5 years, and peaking at 58.4% after 10 years. Median time to recurrence for the patient population on ET was 7.76 years. OS rate for patients on ET was 94.6% at 5 years and 78.3% at 10 years. CONCLUSIONS: This study highlights the high unmet need in stage II and stage III breast cancer, with 1 patient out of 3 recurring after 5 years, and more than half recurring after 10 years despite adjuvant treatment with ET alone. This highlights the need for more effective and tolerable treatment options to address disease recurrence in both the short and long term for eBC HR+/HER2- patients in Canada.
BACKGROUND: Treatment decisions for metastatic colorectal cancer (mCRC) require patients to balance survival benefits, health-related quality of life (HRQoL), and potential risks of side effects while also factoring in their own preferences for different treatment options. Despite growing interest, quantitative patient preferences are not yet integrated into health technology assessments (HTAs) for drug reimbursement recommendations. OBJECTIVES: The Colorectal Cancer Canada's Patient Values Project aims to explore approaches to incorporate quantitative patient preferences into cancer treatment HTA decision-making processes. As a first step, we elicited the treatment preferences and risk tolerance of patients with mCRC in Canada using a multi-method approach. METHODS: We developed a preference survey that included two discrete choice experiments (DCEs) and case 1 best-worst scaling (BWS-1) to estimate preferences for mCRC treatments. DCE1 included change in HRQoL and overall survival as attributes, and treatment attributes in DCE2 were administration and frequency, side effects (nausea, pain, diarrhea), and progression-free survival. The BWS-1 included 25 attributes of potential mCRC treatment side effects based on the cancer-specific quality-of-life questionnaire. The survey was administered across Canada to patients with mCRC aged ≥ 18 years with a self-reported diagnosis of mCRC through patient organizations, cancer centers, and an online panel. Data were analyzed using mixed logit and latent class models (DCEs) and count-based analysis (BWS-1). RESULTS: Overall, 127 patients with mCRC completed the full survey (n = 143 fully completed DCE1, n = 108 fully completed DCE2, n = 127 fully completed BWS-1). Relative preferences for the treatment attributes in the study were consistent with the expectation that better clinical outcomes were preferred over worse clinical outcomes. In DCE1, patients valued both overall survival (24 vs. 12 months) and HRQoL (improvement to 90 vs. worsens to 50 out of 100) as almost equally important. In DCE2, patients preferred better outcomes (longer progression-free survival and no side effects) over worse outcomes, with a disutility for oral capsules/pills compared with intravenous infusions. Significant preference heterogeneity was observed depending on experiences with CRC treatments, treatment side effects, and health status. In the BWS-1, "need help with eating, dressing, washing yourself or using the toilet", "vomiting", and "pain" were ranked as the least and "need to rest", "trouble doing strenuous activities", and "feel tired" as the most tolerable side effects. CONCLUSIONS: This study highlights the value of a multi-method approach in comprehensively assessing treatment preferences and risk tolerance in mCRC. By triangulating multiple preference-elicitation methods, our findings offer a more robust foundation for integrating patient perspectives into Canada's HTA framework. These results will inform the next step of the Colorectal Cancer Canada's Patient Values Project, which aims to explore approaches to explicitly incorporate patient preferences alongside clinical and economic evidence into the cancer treatment HTA decision-making process in Canada.
AIM: Immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies (MAbs) alone or in combination form the backbone of multiple myeloma (MM) treatment, yet MM remains incurable requiring further lines of therapy (LOT). This study investigated real-world treatment patterns, clinical outcomes, and healthcare utilization among triple-class exposed (TCE) patients initiating subsequent LOTs. METHODS: TCE patients receiving additional LOTs (January 2012-December 2022) in the Alberta Health System databases were included. RESULTS: Median age among 221 TCE patients requiring subsequent LOT was 70 years. MAbs (42%) and IMiDs (51%) were the most common drug classes incorporated as first and second LOT, respectively. After first LOT, attrition rate was 32%. From first LOT, median time to next treatment or death (TTNT-D) was 10.1 (95% confidence interval: 8.4-13.3) months, median TTNT was 18.1 (15.6-22.4) months and overall survival was 18.7 (16.0-24.3) months. Within first year of subsequent LOT, patients had a median of 1 emergency department visit, 1 hospitalization, 33 clinic visits, 4 infusion appointments, 37 unique healthcare encounters, and a mean of 32 days spent on laboratory tests. CONCLUSION: Treatment for TCE patients has limited effectiveness and a high healthcare system burden, emphasizing the unmet need for therapies with novel mechanisms of action.
Real-world evidence (RWE) from outside Canada or the UK is sometimes included in submissions to health technology assessments by Canada's Drug Agency/L'Agence des médicaments du Canada (CDA-AMC) and National Institute for Health and Care Excellence when local data are lacking, particularly in rare diseases. However, differences in population demographics, healthcare systems and clinical practice patterns between different jurisdictions can pose challenges for contextualizing nonlocal data for health technology assessments. This primer outlines the challenges of using nonlocal RWE for decision-making, presents assumptions necessary for transportability of RWE, and describes quantitative methods to address these challenges. This primer is written for a broad audience, including industry stakeholders, researchers and clinicians, who are seeking accessible guidance on the use of nonlocal RWE and developments in the field of transportability.
BACKGROUND: Population-based data from real-world sources on metastatic breast cancer (mBC) patient outcomes by HER2 status are limited, particularly in Canada. To meet this need, we examined treatment patterns, outcomes, and healthcare resource utilization in HER2-positive (HER2+) mBC in a real-world Canadian setting. PATIENTS AND METHODS: This retrospective longitudinal cohort consisted of all patients in Alberta, Canada diagnosed with de novo metastatic or recurrent HER2+ breast cancer between 2010 and 2019. Patient data were obtained from the provincial cancer registry, electronic medical records, and other administrative databases. RESULTS: 758 patients with HER2+ mBC were included, of which 461 (60.8 %) were recurrent cases. Taxane + trastuzumab + pertuzumab was the most frequent (61.7 %) first-line regimen, trastuzumab emtansine (T-DM1) was the most frequent (74.8 %) second-line regimen, and capecitabine + lapatinib was the most frequent (52.9 %) third-line regimen. Median overall survival from first-, second-, and third-line chemotherapy was 41.9 months (95 % CI: 36.9-51.2), 18.8 months (95 % CI: 15.4-24.3), and 12.9 months (95 % CI: 11.0-16.8), respectively, with no meaningful differences between de novo and recurrent patients. CONCLUSION: Uptake of guideline-recommended regimens in each line of therapy was lower in recurrent patients although survival was similar to de novo patients. These findings highlight the need for consensus on treatment regimens for de novo and recurrent HER2+ patients, effective first-and second-line management, and novel therapies to improve outcomes. MICROABSTRACT Our study evaluated real-world treatment patterns, clinical outcomes, and healthcare utilization in HER2-positive metastatic breast cancer (mBC) in Alberta, Canada. Among 758 patients, survival was similar between new diagnoses and recurrent cases, despite lower uptake of guideline-recommended therapies in recurrent patients. Our findings highlight the need for consensus on treatment strategies and novel therapies to improve mBC outcomes.
OBJECTIVE: To describe first-line treatment patterns and factors impacting survival for patients with primary advanced (stage III-IV) or recurrent (A/R) endometrial cancer (EC) in Canada. METHODS: This retrospective cohort study used health administrative data for patients with primary A/R EC (2010-2020) in Alberta, Canada. Characteristics by receipt of first-line systemic therapy were compared. Factors impacting overall survival (OS) after first-line chemotherapy were evaluated using a multivariable Cox proportional hazards model. RESULTS: Of 1185 patients included, 817 (68.9%) received first-line systemic therapy (advanced, n = 679 of 885; recurrent, n = 138 of 300). Patients in this cohort were generally younger, with fewer comorbidities than those who did not receive first-line systemic therapy. Patients with recurrent disease who received previous chemotherapy and who had a longer time to recurrence were more likely to receive first-line systemic therapy. The median OS was 53.5 months (95% CI 37.8-80.1); the OS was shorter with older age (≥75 vs. <65 years, adjusted hazard ratio [aHR] 1.62; 95% CI 1.18-2.23) and high-grade versus low-grade histology (aHR 1.99; 95% CI 1.59-3.67). The OS was longer in patients in stage III who had surgery (aHR 0.35; 95% CI 0.24-0.51). CONCLUSION: Characteristics such as age and comorbidities impacted first-line systemic therapy use in primary A/R EC. Patients who were older, with high-grade histology, stage IV without surgery, and receiving platinum monotherapy had the shortest OS. Effective treatment options are needed to prolong survival for primary A/R EC.