Search Results (17)

(1) Background: Cancer is the leading cause of death in Canada, with significant resource limitation impacting the delivery of cancer care nationwide. The onset of the COVID-19 pandemic forced additional resource restriction and diversion, further impacting care delivery. Our intention is to analyze the impact COVID-19 on a provincial medical oncology workload and bring attention to the limitations of the current workload metric for oncologists. (2) Methods: All medical oncology patient encounters were extracted and compared, collected by year and encounter type, from April 2014 through March 2022. (3) Results: There was an increase in all patient encounters by an average of 9.5% per year, including during the strictest COVID-19 restrictions. There was an increase in virtual care encounters from 37.9% to 52.1%. (4) Conclusions: Medical Oncology workloads have increased over time and estimates suggest growing demand. Little data exist to inform workforce requirements and actual workload is not captured by the current metric. Though volume of new consults continues to increase, COVID-19 has highlighted additional changes in the delivery of care, likely with lasting impact, little of which are included in the current workload metric. Full article

Background: Adjuvant zoledronic acid (ZA) appears to improve disease-free survival (DFS) in women with early-stage breast cancer and low levels of estrogen (LLE) because of induced or natural menopause. Characterizing the cost–utility (CU) of this therapy could help to determine its role in clinical practice. Methods: Using the perspective of the Canadian health care system, we examined the CU of adjuvant endocrine therapy with or without ZA in women with early-stage endocrine-sensitive breast cancer and LLE. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (QALYS) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the DFS and fracture benefits of adjuvant ZA. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters. Results: Compared with a no-ZA strategy, adjuvant ZA in the induced and natural menopause groups was associated with, respectively, $7,825 and $7,789 in incremental costs and 0.46 and 0.34 in QALY gains for CU ratios of $17,007 and $23,093 per QALY gained. In one-way sensitivity analyses, the results were most sensitive to changes in the ZA DFS benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant ZA being a cost-effective strategy at a threshold of $100,000 per QALY gained. Conclusions: Based on available data, adjuvant ZA appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and LLE, having cu ratios well below accepted thresholds. Full article

The PI3K/Akt/mTOR (phosphatidylinositol 3 kinase/ Akt/mammalian target of rapamycin) signalling pathway is an established driver of oncogenic activity in human malignancies. Therapeutic targeting of this pathway holds significant promise as a treatment strategy. Everolimus, an mtor inhibitor, is the first of this class of agents approved for the treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer. Everolimus has been associated with significant improvements in progression-free survival; however, it is also associated with increased toxicity related to its specific mechanism of action. Methods: A comprehensive review of the literature conducted using a focused medline search was combined with a search of current trials at http://ClinicalTrials.gov/. Summary tables of the toxicities of the various classes of PI3K/Akt/mTOR inhibitors were created. A broad group of Canadian health care professionals was assembled to review the data and to produce expert opinion and summary recommendations for possible best practices in managing the adverse events associated with these pathway inhibitors. Results: Differing toxicities are associated with the various classes of PI3K/Akt/mTOR pathway inhibitors. The most common unique adverse events observed in everolimus clinical trials in breast cancer include stomatitis (all grades: approximately 60%), noninfectious pneumonitis (15%), rash (40%), hyperglycemia (15%), and immunosuppression (40%). To minimize grades 3 and 4 toxicities and to attempt to attain optimal outcomes, effective management of those adverse events is critical. Management should be interdisciplinary and should use approaches that include education, early recognition, active intervention, and potentially prophylactic strategies. Discussion: Everolimus likely represents the first of many complex oral targeted therapies for the treatment of breast cancer. Using this agent as a template, it is essential to establish best practices involving and integrating multiple disciplines for the management of future PI3K/Akt/mTOR signalling pathway inhibitors. Full article

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2–) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients—efect, sofea, confirm, and bolero-2—have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2– advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient’s age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged. Full article

Background: Treatment uptake and elapsed times along the care path have emerged as potential quality indicators for cancer care delivery. This retrospective study examined changes in adjuvant chemotherapy uptake and elapsed times along the care path for patients in 2005 and in 2007 who had early-stage non-small-cell lung cancer (nsclc) and who underwent curative-intent surgery in Nova Scotia, Canada. Methods: All patients who underwent curative-intent surgery for stages i–iii nsclc in the two years of interest were included. Logistic regression and general linear models were used to examine factors associated with chemotherapy uptake patterns and, at various resolutions (low, intermediate, high), elapsed times between all care events in the care path. Results: In the 223 patients who underwent curative-intent surgery (108 in 2005, 115 in 2007), several factors were associated with uptake patterns and elapsed times. Cohort year (2007 vs. 2005) was not associated with referral to medical oncology [odds ratio (or): 1.05; 95% confidence interval (ci): 0.51 to 2.15; p = 0.905], but it was associated with less treatment after referral (or: 0.34; 95% ci: 0.11 to 1.00; p = 0.057) and less overall uptake (or: 0.35; 95% ci: 0.13 to 0.95; p = 0.040). Patients were referred sooner to medical oncology in 2007 than in 2005 (21 days vs. 35 days, p = 0.008), but experienced longer waits between consultation and chemotherapy delivery (18 days vs. 7 days, p = 0.001). Conclusions: Significant differences were observed in care patterns over time. Frequent monitoring of care patterns at high resolution may optimize insights into emerging trends within cancer care systems. Full article

Purpose: The adoption of a chemotherapeutic regimen in oncologic practice is a function of both its clinical and its economic impacts on cancer management. For breast cancer, U.S. Oncology trial 9735 reported significant improvements in disease-free and overall survival favoring adjuvant tc (docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles) compared with ac (doxorubicin 60 mg/ m2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles). We carried out an economic evaluation to examine the cost–utility of adjuvant tc relative to ac, in terms of cost per quality-adjusted life year (qaly) gained, given the improved breast cancer outcomes and higher costs associated with the tc regimen. Methods: A Markov model was developed to calculate the cumulative costs and qalys gained over a 10-year horizon for hypothetical cohorts of women with breast cancer treated with ac or with tc. Event rates, costs, and utilities were derived from the literature and local resources. Efficacy and adverse events were based on results reported from U.S. Oncology trial 9735. The model takes a third-party direct payer perspective and reports its results in 2008 Canadian dollars. Costs and benefits were both discounted at 3%. Results: At a 10-year horizon, tc was associated with $3,960 incremental costs and a 0.24 qaly gain compared with ac, for a favorable cost–utility of $16,753 per qaly gained. Results were robust to model assumptions and input parameters. Conclusions: Relative to ac, tc is a cost-effective adjuvant chemotherapy regimen, with a cost-effectiveness ratio well below commonly applied thresholds. Full article

Breast cancer positive for HER2 (human epidermal growth factor receptor 2) is associated with a poor prognosis for patients with both early-stage and metastatic breast cancer. Trastuzumab has been shown to be effective and is now considered the standard of care for early-stage patients with HER2-positive breast cancer. In that population, trastuzumab has been studied in six randomized clinical trials. Overall, use of this agent leads to a significant reduction in risk of disease recurrence and improvement in overall survival. Despite the strong evidence for the use of trastuzumab in managing HER2-positive early breast cancer (EBC), a number of clinical controversies remain. The authors of this paper undertook a review of the available scientific literature on adjuvant trastuzumab to produce practical considerations from Canadian oncologists. The panel focused their discussion on five key areas: (1) Management of node-negative disease with tumours 1 cm or smaller in size; (2) Management of HER2-positive EBC across the spectrum of the disease (that is, nodal and steroid hormone receptor status, tumour size); (3) Timing of trastuzumab therapy with chemotherapy for early-stage disease: concurrent or sequential; (4) Treatment duration of trastuzumab for EBC; (5) The role of non-anthracycline trastuzumab-based regimens. Full article

Background: Despite recommendations favouring review of cancer pathology specimens for patients being treated at an institution other than the one that produced the initial pathology report, data regarding discordance rates and their potential clinical impact remain limited, particularly for breast cancer. At the QEII Health Sciences Centre in Halifax, Nova Scotia, it was routine practice to review histopathology when patients referred for adjuvant therapy had undergone their breast cancer surgery and pathology reporting at another institution. The aim of the present study was to determine the rate and clinical impact of discordance in inter-institutional pathology consultations for breast cancer in Nova Scotia. Methods: We conducted a retrospective review of 100 randomly selected inter-institutional pathology consultations for breast cancer patients referred to the QEII in 2004. Cases were categorized as having either no discordance, discordance with no clinical impact, or discordance with potential for clinical impact. Cases with potential clinical impact were independently reviewed by 2 medical oncologists and 2 radiation oncologists, and the discordances were rated as having high, medium, or no clinical impact. Results: The study cohort consisted of 93 cases that met the inclusion criteria. Of these 93 cases, 6 had no discordance, 7 had discordance with no clinical impact, and 80 had discordance with potential for clinical impact. Overall, 10 cases (11%) were rated as having either high or medium clinical impact, with agreement on the clinical impact ratings by oncologist reviewers in the same specialty. The remaining cases had either no clinical impact or disagreement on the clinical impact rating. Conclusions: Inter-institutional pathology consultations for breast cancer in Nova Scotia identified discordant findings with potential clinical impact as determined by oncologist reviewers. Further evaluation of inter-institutional pathology consultations and the impact on clinical decision-making is warranted. Full article

Women receiving neoadjuvant systemic therapy for primary operable or inoperable breast cancer can potentially benefit in a number of ways, but the main advantage, which has been consistently demonstrated, is improved tumour resectability. Given the improvement in outcomes with the adjuvant use of trastuzumab in patients with early-stage breast cancer positive for the human epidermal growth factor receptor 2 (her2), questions have been raised about the use of trastuzumab in the neoadjuvant setting. The present paper reviews the currently available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other her2-targeted agents in the neoadjuvant setting. The panel focussed on (1) the use of trastuzumab and other her2-targeted agents as neoadjuvant therapy in primary operable, locally advanced, and inflammatory breast cancer; and (2) possible choices of chemotherapeutic regimens with trastuzumab. The suggestions described here will continue to evolve as data from current and future trials with trastuzumab and other her2-targeted agents emerge. Full article

The role of targeted therapies in the treatment of women with breast cancer has been rapidly evolving. Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor 2 (her2), was the first her2-targeted therapy that clearly demonstrated a significant clinical benefit for women with her2-overexpressing metastatic breast cancer (mbc). However, in recent years it has become increasingly apparent that, when trastuzumab is used in the first-line setting in combination with chemotherapy, most women eventually develop progressive disease. Determining the treatment options available to women who have progressed while on trastuzumab therapy has been hampered by a paucity of high-quality published data. In addition, with the standard use of trastuzumab in the adjuvant setting (for eligible her2-positive patients), the role of anti-her2 agents for patients who experience a breast cancer relapse has become a clinically relevant question. This manuscript reviews current available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other her2-targeted agents in two key mbc indications: (1) Treatment for women with her2-positive mbc progressing on trastuzumab (that is, treatment beyond progression); (2) Treatment for women with her2-positive mbc recurring following adjuvant trastuzumab (that is, re-treatment). The suggestions set out here will continue to evolve as data and future trials with trastuzumab and other her2-targeted agents emerge. Full article

The epidermal growth factor receptor (EGFR) is often overexpressed or dysregulated in a variety of solid tumours, including gastrointestinal (GI) malignancies. Agents targeting the EGFR-mediated signalling pathway are increasingly part of the therapeutic armamentarium for the treatment of advanced lung, head-and-neck, and colorectal carcinoma. The EGFR inhibitors (EGFRIS) approved in Canada include the tyrosine kinase inhibitors erlotinib and gefitinib (in selected cases), and the monoclonal antibodies (mAbs) panitumumab and cetuximab. Although EGFRIS have been proven effective in the treatment of a variety of malignancies, the entire class of agents is associated with a high prevalence of dermatologic side effects, most commonly skin rash. This reversible condition requires intervention in approximately one third of patients. A proactive, multidisciplinary approach to management can help to improve skin rash and optimize clinical outcomes by preventing EGFRI dose reduction or discontinuation. In addition, effective management and patient education may help to alleviate the significant social and emotional anxiety related to this manageable side effect, thus resulting in improved quality of life. The present article focuses on EGFR-targeted mAbs for the treatment of GI malignancy, addressing the pathophysiology, clinical presentation, and incidence of skin rash caused by this class of agents. Recommendations aimed at establishing a framework for consistent, proactive management of skin rash in the Canadian setting are presented. Full article

Objective: Monoclonal antibodies (MAbs) such as trastuzumab and bevacizumab have become important yet expensive components of systemic cancer therapy across a variety of disease sites. We assessed the potential cost implications of adopting trastuzumab and bevacizumab therapy in the context of their potential utilization in breast, lung, and colorectal cancers. Design: We first estimated MAb costs per patient and treatment indication and then included the MAb acquisition cost and the costs of medical resource utilizations required for therapy delivery. Drug costs were based on 2005 average Canadian wholesale prices, assuming full drug delivery and uncomplicated cycles. A direct-payer perspective was undertaken, and results are reported in Canadian dollars. Potential lifetime costs were then derived according to constructed schema, which account for absolute numbers of target patients and systemic therapy utilization. We subsequently estimated costs of MAb therapy relative to total costs of conventional management without MAb therapy. Results: Trastuzumab costs $49,915 and $28,350 per patient treated in the adjuvant and metastatic breast cancer settings, respectively; bevacizumab costs $48,490 and $39,614 per patient treated in the metastatic lung and colorectal cancer settings, respectively. Potential lifetime absolute costs to Canada’s health care system were approximately $127 million and $299 million for trastuzumab and bevacizumab respectively, corresponding to an average increase in health care expenditure of approximately 19% for breast cancer and 21% for lung and colorectal cancer over conventional management without MAbs. Conclusions: Novel Mab-based therapies such as trastuzumab and bevacizumab will likely add a significant cost burden to Canada’s publicly funded health care system. Full article