Custo-utilidade de terapias-alvo comparadas à dacarbazina para o tratamento de primeira linha do melanoma avançado não-cirúrgico e metastático no Sistema Único de Saúde do Brazil.

OBJECTIVE: To estimate the incremental cost-utility ratio (ICUR) of isolated and combined targeted therapy regimens compared to dacarbazine for first-line treatment of advanced and metastatic melanoma with BRAF V600 mutation. METHODS: A Markov model with three health states (no progression, progression and death), monthly duration cycle and 10-year time horizon was constructed to compare targeted therapy regimens (vemurafenib, dabrafenib, vemurafenib/cobimetinib and dabrafenib/trametinib) with dacarbazine chemotherapy under the Brazilian public health perspective. One-way and probabilistic sensitivity analyses were performed. RESULTS: Mean cost was R$5662.50 ($1490.13) for dacarbazine, R$175 937.18 (46 299.26) for vemurafenib, R$167 461.70 ($44 068.87) for dabrafenib, R$425 901 ($112 079.21) for vemurafenib/cobimetinib and R$411 799.81 ($108 368.37) for dabrafenib/trametinib, whereas QALY was 0.91 for dacarbazine, 1.08 for vemurafenib, 1.12 for dabrafenib, 1.64 for vemurafenib/cobimetinib and 1.56 for dabrafenib/trametinib. The ICUR was estimated from R$572 165.76 ($150 569.94) to R$1 012 524.56 ($266 453.83) per patient, and the most impactful parameters were risk of progression and death, and treatment cost. CONCLUSION: The incorporation of targeted therapies in the Brazilian public health system would produce an additional expenditure of at least 19 times the national GDP per capita to increase in one year the quality-adjusted survival of each patient with advanced/metastatic BRAF-mutant melanoma.

Non-aspirin non-steroidal anti-inflammatory drugs for the primary chemoprevention of non-gastrointestinal cancer: summary of evidence.

BACKGROUND: There is evidence that aspirin is effective for the chemoprevention of colorectal cancer. Due to their similar pharmacodynamics, the use of other non-steroidal anti-inflammatory drugs (NSAIDs) has been suggested for other cancer sites. Although this possibility has been discussed in the literature, uncertainty remains about the actual effects of NSAIDs other than aspirin in nongastrointestinal cancer. OBJECTIVE: To summarize the best available evidence of the primary chemopreventive effects of non-aspirin NSAIDs for nongastrointestinal cancer. METHODS: Our inclusion criteria were narrative or systematic reviews, clinical guidelines and, if they had not been previously included, primary controlled studies that evaluated the effectiveness of non-aspirin NSAIDs in preventing non-gastrointestinal cancer in healthy individuals. Studies were retrieved from the following databases: Guidelines.gov, BMJ Clinical Evidence, TRIP database, UpToDate, MEDLINE, CANCERLIT, Embase, CINAHL, ISI Web of Science and Scopus. Two independent reviewers selected eligible studies. Data were extracted by one reviewer and crosschecked by two others. RESULTS: We found 9,984 non-duplicated articles and included 56 eligible studies. Most of these studies were observational. The studies reported conflicting results or no statistically significant associations between the use of non-aspirin NSAIDs and risk of lung, ovary, bladder, prostate, skin, and head and neck cancers. In contrast, an increased risk of renal cell carcinoma and a reduced risk of breast cancer were found to be statistically significant. The included studies had methodological limitations, which reduces our confidence in their results. CONCLUSIONS: We did not find sufficient evidence to support the use of the non-aspirin NSAIDs for the primary chemoprevention of a wide variety of non-gastrointestinal cancers. This scenario suggests caution when considering the routine use of non-aspirin NSAIDs. Additional well-conducted controlled studies may provide more conclusive evidence on this issue, but there are concerns about the risks of such exposure.