6597 Background: Determination of health preference is a common outcome measure used in economic evaluations and represents the societal valuation of the patient's health state. It can be measured with generic multi-attribute instruments. Multi-attribute health preference (HP) instruments have similar domains to oncology quality of life (QOL) instruments. It is possible that HP instruments may over or under estimate a patient's QOL. Methods: Consecutive breast cancer patients irrespective of stage and treatment attending an outpatient clinic were approached to enrol in a work productivity and QOL study. The Functional Assessment of Cancer Therapy- General (FACT-G) / -Breast (FACT-B), and the EQ-5D were used to assess QOL and HP, respectively. Total scores are 108 (FACT-G) and 148 (FACT-B). EQ-5D is a generic, multi-attribute instrument measuring health preference from 0 to 1 for 243 possible health states. The analysis was carried out post-hoc to investigate the ceiling effect with the EQ-5D and FACT. Results: A total of 151 patients with breast cancer participated in the study. Mean±SD age was 55.2±12.5 years and time since diagnosis ranged from 0.1 to 25.0 years. Mean±SD FACT-G and FACT-B scores were 79.3±16.6 and 105.2±21.6, respectively. A perfect score was observed in only one patient for the FACT-G, none for the FACT-B, and in 35 (23.2%) patients for the EQ-5D. Four EQ-5D health states accounted for half the sample, with perfect health being the most common. Mean±SD utility score was 0.80±0.16. A correlation test between the EQ-5D and both FACT scores demonstrated convergent validity (p<0.01). Conclusions: Ceiling effect was observed with the EQ-5D which has fewer questions and a smaller scale compared to the FACT. This may indicate that the EQ-5D is not as sensitive in a general breast cancer population. However, the mean utility score was comparable to other studies in women with breast cancer. Future studies should investigate the relationship between long term QOL and HP in a larger cohort of women with breast cancer taking into account disease stage and treatment strategy. No significant financial relationships to disclose.
e15180 Background: ZOL therapy is associated with severe (i.e., grade ≥ 3) hypocalcemia and hypophosphatemia in a subset of patients with metastatic CRPC. However, as opposed to the distinct clinical picture of hypocalcemia, the symptoms of hypophosphatemia are less pathognomonic. Furthermore, serum phosphate abnormalities are not regularly reported. Methods: To characterize the rate and clinical impact of severe hypophosphatemia in CRPC patients undergoing ZOL therapy, we identified CRPC patients receiving at least 3 doses of ZOL at our Centre between 01/2004 and 03/2011. Patient demographics, disease characteristics and laboratory parameters were extracted using the Oncology Symptom Control and Information Resource database, and by means of manual chart review. Results: 12 of 90 evaluable patients developed grade ≥ 3 hypophosphatemia (nadir) after 364±299 days (mean±SD) following the first dose of ZOL. While only one patient presented with concomitant severe hypocalcemia, the hypophosphatemia nadir coincided with rising PSA readings in 9 out of 11 informative patients. Severe ZOL-associated hypophosphatemia identified patients with worse outcome (median overall survival from time of CRPC diagnosis to death 685 days) compared to patients without documented hypophosphatemia (907 days, HR 0.52, p=0.049; n=42), or patients with grade 1-2 hypophosphatemia (1035 days, HR 0.44, p=0.016; n=36). Otherwise, the prognostic nomogram developed by Armstrong et al appears not to capture the poor prognosis of patients with severe ZOL-associated hypophosphatemia. Conclusions: Grade 3-4 hypophosphatemia occurs in about 15% of CRPC patients undergoing ZOL therapy and is associated with worse prognosis when compared to patients with absent or mild hypophosphatemia. The latter is usually transient and likely related to increased parathyroid hormone levels due to calcium decreases as a consequence of bisphosphonate therapy. On the other hand, the distinct clinical behavior of CRPC presenting with ZOL-associated severe hypophosphatemia suggests that secreted tumor-associated factors such as fibroblast growth factor 23 may contribute to this phenomenon.
BackgroundFebrile neutropenia is a serious toxicity of cancer chemotherapy that is usually treated in hospital. We assessed the cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against febrile neutropenia in diffuse large B-cell lymphoma (DLBCL) patients undergoing chemotherapy.
6531 Background: Previously we have shown that the incremental cost effectiveness ratio (ICER) of erlotinib, in unselected patients with advanced non-small cell lung cancer (NSCLC) after chemotherapy failure, was $95,869 (2007 CAD), per life year gained (LYG), using original patient data from the NCIC CTG BR.21 trial of erlotinib versus placebo in advanced NSCLC. Here, we investigate the value of combining clinical and molecular predictors of outcome to identify more, and less cost- effective patient subgroups for treatment. Methods: Cost-effectiveness ranges of interest were identified a priori: group A ICER <$50,000/LYG, B $50,000- 75,000/LYG and C >$200,000/LYG CAD. Significant clinical and molecular predictors of outcome from the BR.21 trial were assessed to identify groups within these thresholds of cost-effectiveness, and to characterize patient characteristics of each group that had >50 patients. Due to small numbers, EGFR mutation status was not included. Results: The subgroup with lowest ICER ($22,564/LYG; n=52) consisted of patients with adenocarcinoma, never smoker status who had received one prior chemotherapy regimen. By contrast, past and present smokers with wild-type EGFR and K-ras gene mutation had the highest ICER for erlotinib treatment ($3,862,962/LYG; n=52). The presence of one of the following variables, never smoking status, high EGFR copy number or EGFR protein positive tumours (immunohistochemistry), predicted for lower ICERs in groups A and B, irrespective of histological subtype. Female gender was associated with higher ICERs in all three groups. Conclusions: Incorporation of molecular and clinical predictors into economic analyses has the potential to differentiate cost-effective versus cost-ineffective subgroups for treatment. We identified subsets of patients (e.g. smoking history, non-adenocarcinoma histology) who could be treated within a reasonable range of cost effectiveness. While subset analyses must be interpreted with caution, examining different methodological approaches in the economic analysis of novel agents is warranted and a parallel investigation using classification and regression tree methodology is underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche and OSIP Roche, Roche and OSIP
The National Cancer Institute of Canada Clinical Trials Group CO.17 study showed that patients with advanced colorectal cancer had improved overall survival when cetuximab, an epidermal growth factor receptor-targeting antibody, was given in addition to best supportive care. We conducted a cost-effectiveness analysis using prospectively collected resource utilization and health utility data for patients in the CO.17 study who received cetuximab plus best supportive care (N = 283) or best supportive care alone (N = 274).Direct medical resource utilization data were collected, including medications, physician visits, toxicity management, blood products, emergency department visits, and hospitalizations. Mean survival times for the study arms were calculated for the entire population and for the subset of patients with wild-type KRAS tumors over an 18- to 19-month period. All costs were presented in 2007 Canadian dollars. One-way and probabilistic sensitivity analysis was used to determine the robustness of the results. Cost-effectiveness acceptability curves were determined. The 95% confidence intervals (CIs) for the incremental cost-effectiveness ratios and the incremental cost-utility ratios were estimated by use of a nonparametric bootstrapping method (with 1000 iterations).For the entire study population, the mean improvement in overall and quality-adjusted survival with cetuximab was 0.12 years and 0.08 quality-adjusted life-years (QALYs), respectively. The incremental cost with cetuximab compared with best supportive care was $23,969. The incremental cost-effectiveness ratio was $199,742 per life-year gained (95% CI = $125,973 to $652,492 per life-year gained) and the incremental cost-utility ratio was $299,613 per QALY gained (95% CI = $187,440 to $898,201 per QALY gained). For patients with wild-type KRAS tumors, the incremental cost with cetuximab was $33,617 and mean gains in overall and quality-adjusted survival were 0.28 years and 0.18 QALYs, respectively. The incremental cost-effectiveness ratio was $120,061 per life-year gained (95% CI = $88,679 to $207,075 per life-year gained) and the incremental cost-utility ratio was $186,761 per QALY gained (95% CI = $130,326 to $334,940 per QALY gained). In a sensitivity analysis, cetuximab cost and patient survival were the only variables that influenced cost-effectiveness.The incremental cost-effectiveness ratio of cetuximab over best supportive care alone in unselected advanced colorectal cancer patients is high and sensitive to drug cost. Incremental cost-effectiveness ratios were lower when the analysis was limited to patients with wild-type KRAS tumors.
e17572 Background: Economic evaluations (EE) are routinely used by decision-makers in Canada. CADTH's “Guidelines for the Economic Evaluation of Health Technologies: Canada” Third edition, 2006, provide guidance on the conduct of EEs for all therapeutic products. The consistency and quality of oncology EEs are variable and therapeutics in the cancer care environment presented unique challenges in decision making. Several chapters of the CADTH document adequately defined methods for the conduct of an oncology EE. However, some chapters required more specific guidance to improve the quality of oncology EEs. The goal was to provide direction on methods for the conduct of high quality EEs in oncology. Methods: The Working Group on Economic Analysis, NCIC CTG and CADTH jointly initiated this project and formed a working group (WG) of oncologists, health economists, decision makers and economic analysts. The WG identified CADTH chapters where oncology-specific guidance would be required. In-person and teleconference meetings provided content and structure for the document. Formal reviews by external academic experts, cancer agencies, patient groups and the pharmaceutical industry were conducted. Feedback was reviewed by the WG and incorporated as appropriate. Results: Chapters requiring guidance included: target population, comparators, perspective, effectiveness, modeling, type of evaluation, valuing health, time horizon, costs and resources, sensitivity analysis and equity. Guidance included clarity around CADTH methodology and recommendations for oncology products. For example for the effectiveness chapter, there was guidance around the use of intermediate outcomes (progression free survival vs. overall survival) and type of evidence (phase II vs. phase III). Overall recommendations for chapters will be presented. Conclusions: The oncology adapted economic guidelines provide specific guidance on the conduct of EEs for oncology products and will be published as an addendum to CADTH's third edition document. Their use should lead to more consistent application of EE methodologies for anti-cancer drugs and higher quality information for decision-makers at a national and perhaps international level. No significant financial relationships to disclose.
