Cost-effectiveness analysis of neoadjuvant pertuzumab and trastuzumab therapy for locally advanced, inflammatory, or early HER2-positive breast cancer in Canada.

OBJECTIVE: The NeoSphere trial demonstrated that the addition of pertuzumab to trastuzumab and docetaxel for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early breast cancer (eBC) resulted in a significant improvement in pathological complete response (pCR). Furthermore, the TRYPHAENA trial supported the benefit of neoadjuvant dual anti-HER2 therapy. Survival data from these trials is not yet available; however, other studies have demonstrated a correlation between pCR and improved event-free survival (EFS) and overall survival (OS) in this patient population. This study represents the first Canadian cost-effectiveness analysis of pertuzumab in the neoadjuvant treatment of HER2-positive eBC. METHODS: A cost-utility analysis (CUA) was conducted using a three health state Markov model ('event-free', 'relapsed', and 'dead'). Two separate analyses were conducted; the first considering total pCR (ypT0/is ypN0) data from NeoSphere, and the second from TRYPHAENA. Published EFS and OS data partitioned for patients achieving/not achieving pCR were used in combination with the percentage achieving pCR in the pertuzumab trials to estimate survival. This CUA included published utility values and direct medical costs including drugs, treatment administration, management of adverse events, supportive care, and subsequent therapy. To address uncertainty, a probabilistic sensitivity analysis (PSA) and alternative scenarios were explored. RESULTS: Both analyses suggested that the addition of pertuzumab resulted in increased life-years and quality-adjusted life-years (QALYs). The incremental cost per QALY ranged from $25,388 (CAD; NeoSphere analysis) to $46,196 (TRYPHAENA analysis). Sensitivity analyses further support the use of pertuzumab, with cost-effectiveness ratios ranging from $9230-$64,421. At a threshold of $100,000, the addition of pertuzumab was cost-effective in nearly all scenarios (93% NeoSphere; 79% TRYPHAENA). CONCLUSION: Given the improvement in clinical efficacy and a favorable cost per QALY, the addition of pertuzumab in the neoadjuvant setting represents an attractive treatment option for HER2-positive eBC patients.

Cost-effectiveness of folfirinox for first-line treatment of metastatic pancreatic cancer.

BACKGROUND: The accord 11/0402 trial demonstrated that folfirinox (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) is significantly more efficacious than gemcitabine monotherapy in the first-line treatment of metastatic pancreatic cancer (mpc). The present study assessed the cost-effectiveness of first-line folfirinox compared with first-line gemcitabine for public payers in Canada. METHODS: A Markov model simulated the movement of mpc patients from first-line treatment until death. Overall survival (os) and progression-free survival (pfs) data were derived from accord. Published utility data and Canadian costs were applied based on time in each health state and on treatment-related adverse event (ae) rates. Costs included first- and second-line therapy, monitoring, and costs to treat aes. Two separate analyses were performed. Analysis 1 was based on trial data [first-line folfirinox followed by second-line gemcitabine compared with first-line gemcitabine followed by second-line platinum-based chemotherapy, with use of granulocyte colony-stimulating factor (g-csf) allowed], and analysis 2 used Ontario treatment patterns before folfirinox funding (first-line folfirinox followed by second-line gemcitabine compared with first-line gemcitabine followed by best supportive care, no use of g-csf). RESULTS: Compared with first-line gemcitabine, first-line folfirinox resulted in more life-years and quality adjusted life-years (qalys). Probabilistic sensitivity analysis results showed that, for analyses 1 and 2 respectively, folfirinox has a greater than 85% probability and an approximately 80% probability of being cost-effective at the $100,000 threshold. CONCLUSIONS: Compared with gemcitabine, first-line folfirinox significantly prolongs median os. Given the favourable cost per qaly, the improvement in clinical efficacy, and the limited available treatment options, folfirinox represents an attractive cost-effective treatment for mpc.

Cost-effectiveness of oxaliplatin in the adjuvant treatment of colon cancer in Canada.

OBJECTIVE: The cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5FU/LV)-the FOLFOX regimen-was compared with that of 5FU/LV alone as adjuvant therapy for patients with stage III colon cancer, from the perspective of the Cancer Care Ontario New Drug Funding Program. In the mosaic (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) trial, the FOLFOX regimen significantly improved disease-free survival. The mosaic trial formed the basis of the present analysis. METHODOLOGY: Extrapolated patient-level data from the mosaic trial were used to model patient outcomes from treatment until death. Utilities were obtained from the literature. Resource utilization data were derived from the mosaic trial and supplemented with data from the literature. Unit costs were obtained from the Ontario Ministry of Health and Long-Term Care, the London Health Sciences Centre, and the literature. RESULTS: Lifetime incremental cost-effectiveness ratios for FOLFOX compared with 5fu/lv were CA$14,266 per disease-free year, CA$23,598 per life-year saved, and CA$24,104 per quality adjusted life-year (QALY) gained, discounting costs and outcomes at 5% per annum. These results were stable for a wide range of inputs; only utility values associated with relapse seemed to influence the cost-effectiveness ratios observed. CONCLUSIONS: With an incremental cost of CA$24,104 per QALY gained, FOLFOX is a cost-effective adjuvant treatment for stage iii colon cancer. Compared with 5fu/lv alone, this regimen offers better clinical outcomes and provides good value for money.

Incremental cost-effectiveness analysis comparing rofecoxib with nonselective NSAIDs in osteoarthritis: Ontario Ministry of Health perspective.

BACKGROUND: Clinical trials have shown rofecoxib, a selective inhibitor of cyclo-oxygenase-2, to be associated with fewer gastrointestinal complications than non-selective nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVE: To evaluate the potential clinical and economic consequences of rofecoxib prescription in Ontario, Canada, for patients with osteoarthritis (OA) aged >65 years who did not respond to paracetamol (acetaminophen) therapy. DESIGN: Decision analytic modelling study. METHODS: A model was constructed to compare rofecoxib and nonselective NSAIDs with respect to their gastrointestinal complications in patients with OA. The model had a 1-year horizon and considered direct medical costs from the perspective of the Ontario Ministry of Health. Event rates were estimated from a pooled analysis of 8 phase IIb/Ill clinical trials. The number of perforations, ulcers and bleeds (PUBs) with each strategy was used as the primary measure of effectiveness. RESULTS: In the base-case scenario, the expected total cost per patient-day on nonselective NSAIDs was 1.60 Canadian dollars (Can dollars) versus 1.67 Can dollars on rofecoxib (1999 values). Rofecoxib was associated with 0.0109 fewer PUBs per patient per year. The incremental cost to avoid 1 additional PUB by substituting rofecoxib for nonselective NSAIDs was 2247 Can dollars. The rofecoxib strategy became dominant if a gastroprotective agent was prescribed to more than 27.5% of the patients receiving nonselective NSAIDs. CONCLUSION: For patients with OA aged >65 years in whom paracetamol therapy has failed, rofecoxib may represent a cost-effective alternative to nonselective NSAIDs. Increased costs for drug acquisition are offset, in part. by avoidance of gastrointestinal complications and reduced use of gastroprotective agents. Rofecoxib may offer increased benefit among patients at a higher risk of serious gastrointestinal events.