Survival outcome differences based on treatments used and knowledge of the primary tumour site for patients with cancer of unknown and known primary in Ontario.

Introduction: Patients with cancer of unknown primary (cup) have pathologically confirmed metastatic tumours with unidentifiable primary tumours. Currently, very little is known about the relationship between the treatment of patients with cup and their survival outcomes. Thus, we compared oncologic treatment and survival outcomes for patients in Ontario with cup against those for a cohort of patients with metastatic cancer of known primary site. Methods: Using the Ontario Cancer Registry and the Same-Day Surgery and Discharge Abstract databases maintained by the Canadian Institute for Health Information, we identified all Ontario patients diagnosed with metastatic cancer between 1 January 2000 and 31 December 2005. Ontario Health Insurance Plan treatment records were linked to identify codes for surgery, chemotherapy, or therapeutic radiation related to oncology. Multivariable Cox regression models were constructed, adjusting for histology, age, sex, and comorbidities. Results: In 45,347 patients (96.3%), the primary tumour site was identifiable, and in 1743 patients (3.7%), cup was diagnosed. Among the main tumour sites, cup ranked as the 6th largest. The mean Charlson score was significantly higher (p < 0.0001) in patients with cup (1.88) than in those with a known primary (1.42). Overall median survival was 1.9 months for patients with cup compared with 11.9 months for all patients with a known-primary cancer. Receipt of treatment was more likely for patients with a known primary site (n= 35,012, 77.2%) than for those with cup (n = 891, 51.1%). Among patients with a known primary site, median survival was significantly higher for treated than for untreated patients (19.0 months vs. 2.2 months, p < 0.0001). Among patients with cup, median survival was also higher for treated than for untreated patients (3.6 months vs. 1.1 months, p < 0.0001). Conclusions: In Ontario, patients with cup experience significantly lower survival than do patients with metastatic cancer of a known primary site. Treatment is associated with significantly increased survival both for patients with cup and for those with metastatic cancer of a known primary site.

The evolution of biosimilars in oncology, with a focus on trastuzumab.

Cancer therapy has evolved significantly with increased adoption of biologic agents ("biologics"). That evolution is especially true for her2 (human epidermal growth factor receptor-2)-positive breast cancer with the introduction of trastuzumab, a monoclonal antibody against the her2 receptor, which, in combination with chemotherapy, significantly improves survival in both metastatic and early disease. Although the efficacy of biologics is undeniable, their expense is a significant contributor to the increasing cost of cancer care. Across disease sites and indications, biosimilar agents are rapidly being developed with the goal of offering cost-effective alternatives to biologics. Biosimilars are pharmaceuticals whose molecular shape, efficacy, and safety are similar, but not identical, to those of the original product. Although these agents hold the potential to improve patient access, complexities in their production, evaluation, cost, and clinical application have raised questions among experts. Here, we review the landscape of biosimilar agents in oncology, with a focus on trastuzumab biosimilars. We discuss important considerations that must be made as these agents are introduced into routine cancer care.

A review of the value of human epidermal growth factor receptor 2 (HER2)-targeted therapies in breast cancer.

The cost of cancer drugs continues to escalate with the rapid development and approval of novel therapies, especially over the course of the last decade. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, the survival benefits gained by new treatments have been undeniably substantial. It is important to assess the financial value of these therapies for decision making at both the societal and individual level. This information is key for managing resources in resource-limited health care systems, while at the same time supporting patient decision-making and conversations between patient and physicians on cost versus benefit. In this article, we perform a systematic review of cost-effectiveness analyses that have been completed to date on HER2-targeted agents, focussing on those that correlate with standard of care therapy. Our discussion also highlights potential strategies to overcome several limitations associated with measuring value for anticancer drugs.

The clinical significance of occult gynecologic primary tumours in metastatic cancer.

OBJECTIVE: We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os). METHODS: We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002-2011. We defined patients as having an "occult" primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have "obvious" primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt. RESULTS: Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women (n = 285 of 2552, 11.2%) than in men (n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours (n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts (n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses. CONCLUSIONS: In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes.

Cost-effectiveness of using a gene expression profiling test to aid in identifying the primary tumour in patients with cancer of unknown primary.

We aimed to investigate the cost-effectiveness of a 2000-gene-expression profiling (GEP) test to help identify the primary tumor site when clinicopathological diagnostic evaluation was inconclusive in patients with cancer of unknown primary (CUP). We built a decision-analytic-model to project the lifetime clinical and economic consequences of different clinical management strategies for CUP. The model was parameterized using follow-up data from the Manitoba Cancer Registry, cost data from Manitoba Health administrative databases and secondary sources. The 2000-GEP-based strategy compared to current clinical practice resulted in an incremental cost-effectiveness ratio (ICER) of $44,151 per quality-adjusted life years (QALY) gained. The total annual-budget impact was $36.2 million per year. A value-of-information analysis revealed that the expected value of perfect information about the test's clinical impact was $4.2 million per year. The 2000-GEP test should be considered for adoption in CUP. Field evaluations of the test are associated with a large societal benefit.

Evaluating the efficacy of current clinical practice of adjuvant chemotherapy in postmenopausal women with early-stage, estrogen or progesterone receptor-positive, one-to-three positive axillary lymph node, breast cancer.

PURPOSE: We evaluated the benefit of the current clinical practice of adjuvant chemotherapy for postmenopausal women with early-stage, estrogen- or progesterone-receptor-positive (er/pr+), one-to-three positive axillary lymph node (1-3 ln+), breast cancer (esbc). METHODS: Using the Manitoba Cancer Registry, we identified all postmenopausal women diagnosed with er/pr+ 1-3 ln+ esbc during the periods 1995-1997, 2000-2002, and 2003-2005 (n = 156, 161, and 171 respectively). Treatment data were obtained from the Manitoba Cancer Registry and by linkage with Manitoba administrative databases. Seven-year survival data were available for the 1995-1997 and 2000-2002 populations. Using Cox regression, we assessed the independent effect of the clinical practice of adjuvant chemotherapy on disease-free (dfs) and overall survival (os). RESULTS: Clinical breast cancer treatments did not differ significantly between the 2000-2002 and 2003-2005 populations. Adjuvant chemotherapy was administered in 103 patients in the 2000-2002 population (64%) and in 44 patients in the 1995-1997 population [28.2%; mean difference: 36%; 95% confidence interval (ci): 31% to 40%; p < 0.0001]. Compared with 1995-1997, 2000-2002 was not significantly associated with an incremental dfs benefit for patients over a period of 7 years (2000-2002 vs. 1995-1997; adjusted hazard ratio: 0.98; 95% ci: 0.64 to 1.4). CONCLUSIONS: The treatment standard of adjuvant chemotherapy in addition to endocrine therapy may not be effective for all women with er/pr+ 1-3 ln+ esbc. There could be a subgroup of those women who do not benefit from adjuvant chemotherapy as expected and who are therefore being overtreated. Further studies with a larger sample size are warranted to confirm our results.