Original Title: Terapia-alvo (vemurafenibe, dabrafenibe, cobimetinibe, trametinibe) e imunoterapia (ipilimumabe, nivolumabe, pembrolizumabe) para o tratamento de primeira linha do melanoma avançado não-cirúrgico e metastático

Authors' objectives: Is the use of targeted therapies or immunotherapies more effective, safe and cost-effective compared with dacarbazine chemotherapy for the first-line treatment of advanced (unresectable and metastatic) melanoma?

Authors' results and conclusions: The Conitec’s members present at the 88th Ordinary Meeting, on July 8th, 2020, unanimously decided to recommend the incorporation of the anti-PD1 agents (nivolumab or pembrolizumab), in the scope of SUS, for the first-line treatment of advanced (unresectable and metastatic) melanoma, in accordance with the SUS model of cancer care. The new price proposals submitted by the manufacturers of the anti-PD1 agents (nivolumab and pembrolizumab), as well as their satisfactory efficacy and safety profiles, were considered. The monthly cost of treatment should be reduced according to a reference value of 3 GDP per capita for a favourable incremental cost-effectiveness ratio. Finally, the possibility of establishing a maximum value for the procedure in the SIGTAP (which stands for Management System of the Table of Procedures, Medicines, Orthotics, Prosthetics and Special Materials), with recommendation of the therapeutic class, was also considered. The Deliberation Record No. 533/2020 was signed.

Authors' recommendations: Scientific evidence: Based on the studies analysed, all these therapies showed a statistically significant superiority compared with standard treatment with dacarbazine, for both Progression-Free Survival (PFS) and Overall Survival (OS) outcomes, except dabrafenib alone. Regarding OS, immuno-combination therapy with nivolumab plus ipilimumab reduced the risk of death by 67% (23% in a worst-case scenario); immuno-monotherapy with nivolumab or pembrolizumab by 54% (41% in a worst-case scenario); targeted combination therapies by 44-46% (23-27% in a worst-case scenario); immuno-monotherapy with ipilimumab by 32% (7% in a worst-case scenario); and targeted monotherapy with vemurafenib by 20% (3% in a worst-case scenario). Grade 3-4 adverse events were assessed for the following therapeutic classes: targeted therapy, immunotherapy, and chemotherapy. A lower risk of adverse events was reported for immuno-monotherapy with anti-PD-1 agents (nivolumab and pembrolizumab) compared with dacarbazine, and the therapeutic classes that showed the highest risk of adverse events were: targeted monotherapy, targeted combination therapy, anti-CTLA-4 immunotherapy, and immuno-combination therapy, with a relative risk above 1.40. Budget impact analysis: The incremental budget impact over 5 years ranged from BRL 617,226,282.43 to BRL 2,880,924,401.13 for ipilimumab and its combination with nivolumab, respectively. Targeted combination therapies resulted in a lower budget impact compared with nivolumab, as in these strategies only half of patients with BRAF mutation would be treated. Medication costs as well as direct costs associated with treatment were considered.

Project Status: Completed

URL for project: http://conitec.gov.br/images/Consultas/Relatorios/EN2020/20210106_Report541_TargetedTherapiesandImmunotherapies_first-linetreatment_Melanoma.pdf

Year Published: 2020

URL for published report: http://conitec.gov.br/images/Relatorios/2020/Relatorio_541_TerapiaAlvo_Melanoma_Final_2020.pdf

URL for additional information: http://conitec.gov.br/recomendation-reports

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Brazil

Organisation Name: National Committee for Technology Incorporation (CONITEC)

Contact Address: Esplanada dos Ministérios, Bl. G, Ed. Sede, 8º andar, CEP: 70058-900

Contact Name: Clarice Moreira Portugal

Contact Email: clarice.portugal@saude.gov.br