Treatment of advanced melanoma - A changing landscape / Tratamento de melanoma avançado - Um panorama em transformação

Summary Following decades of relative ostracism, advances in the treatment of melanoma have brought a new reality for patients, physicians and researchers. While antibodies targeting molecules involved in the modulation of the interaction between melanoma and immune cells changed the meaning of the term "cancer immunotherapy," a better characterization of the molecular aberrations involved in melanoma carcinogenesis prompted the development of inhibitors of the mitogen-activated protein kinase pathway (MAPK) that also led to significant improvements both in response rates and survival. As a result, new drugs have been approved for clinical use in the United States and Europe, including the immune-checkpoint blockers ipilmumab, pembrolizumab and nivolumab, the oncolytic herpesvirus talimogene laherparepvec, and the targeted-agents vemurafenib, dabrafenib, cobimetinib and trametinib. In this article, we review the results of studies that brought new approaches to the bedside and discuss how these developments are being incorporated into the care of patients in Brazil.

Resumo Após décadas de ostracismo, os recentes avanços no tratamento do melanoma trouxeram uma nova realidade para pacientes, médicos e pesquisadores. Enquanto anticorpos monoclonais voltados a moléculas envolvidas na modulação da interação entre células do melanoma e do sistema imune consolidaram o uso da "imunoterapia", um melhor conhecimento acerca das aberrações genômicas envolvidas na carcinogênese do melanoma viabilizaram o desenvolvimento de inibidores da via mitogen-activated protein kinase pathway (MAPK), o que também resultou em ganhos significativos em taxas de resposta e sobrevida. Consequentemente, novas modalidades de tratamento foram aprovadas para uso clínico nos Estados Unidos e na Europa, incluindo os bloqueadores de correceptores imunes ipilimumabe, nivolumabe e pembrolizumabe, o herpesvírus oncolítico talimogene laherparepvec (T-VEC), e os agentes-alvo vemurafenibe, dabrafenibe, cobimetinibe e trametinibe. Nesse artigo, revisamos os resultados que trouxeram novas alternativas para a prática clínica e discutimos a incorporação desses avanços ao cuidado de pacientes no Brasil.

Activity and safety of sunitinib in poor risk metastatic renal cell carcinoma patients

Purpose To assess the activity, safety and treatment patterns of sunitinib in patients with poor-risk metastatic renal cell carcinoma (mRCC). Materials and Methods We retrospectively reviewed the charts of poor risk patients treated with sunitinib from October 2006 to July 2013 who met the eligibility criteria. The primary endpoint was overall survival (OS). Tumor radiological response was measured according to RECIST 1.1 and adverse events (AEs) were assessed through standard criteria. Results Median OS was 8.16 months (95% CI, 5.73-10.59). Of the 53 patients included in this analysis, 9 (17.0%) achieved partial response, 12 (22.6%) had stable disease. Median treatment duration was 3.30 months (95% CI: 1.96-4.63) and 26.4% of patients discontinued treatment due to toxicity. Grade 3 or higher AEs occurred in 39.6% of patients, the most common being fatigue (15.1%), neutropenia (9.5%), nausea, vomiting and diarrhea (7.5% each). Discussion Sunitinib may benefit some unselected poor-risk patients, although the rates of AEs and drug discontinuation suggest a need for careful patient monitoring. .