Patterns of immune-related adverse events in patients treated with immune checkpoint inhibitors: a Brazilian real-world analysis

ABSTRACT

Objectives: To report real-world data of a cohort of patients treated with immune-checkpoint inhibitors in Brazil, with focus in immune-related adverse events.

Material and Methods: In this retrospective study, we analyzed a cohort of patients with metastatic solid tumors treated at an oncology reference center with at least one dose of immune-checkpoint inhibitors (given as monotherapy or in combination with other agents). The safety profile was characterized through the incidence of adverse events, management and hospitalization.

Results: We included 185 patients. Immune-related adverse events were observed in 92 of the 185 study patients (49.7%), including 16 patients (8.6%) with such events of grade 3 or 4, and 28 patients (15.1%) requiring systemic corticosteroid therapy. Thyroid disorders (20%), rash (17.8%), pruritus (11.4%) and colitis (11.4%) were the most frequent immune-related adverse events. Five (2.7%) patients discontinued immune-checkpoint inhibitors and 15 (7.0%) were hospitalized due to immune-related adverse events. Development of immune-related adverse events and immune-checkpoint inhibitors used in the firstline setting were associated with prolonged progression-free survival and overall survival in the multivariate analysis. Moreover, age <75 years old and ECOG score 0 or 1 were positively associated with overall survival in the multivariate analysis.

Conclusion: This study based upon a Brazilian “real-world” data confirms the toxicity profile of immune-checkpoint inhibitors seen in clinical trials. In accordance with previous retrospective analyses, development of immune-related adverse events was associated with survival outcome of immune-checkpoint inhibitors treatment in patients with metastatic solid cancers.

RESUMO

Objetivos: Relatar dados do mundo real de uma coorte de pacientes tratados com inibidores de checkpoint imunológico no Brasil, com foco em eventos adversos relacionados ao sistema imunológico.

Material e Métodos: Neste estudo retrospectivo, analisamos uma coorte de pacientes com tumores sólidos metastáticos tratados em um centro de referência em oncologia com pelo menos uma dose de inibidores de checkpoint imunológico (administrados em monoterapia ou em combinação com outros agentes). O perfil de segurança foi caracterizado pela incidência de eventos adversos, manejo e hospitalização.

Resultados: Incluímos 185 pacientes. Eventos adversos relacionados ao sistema imunológico foram observados em 92 dos 185 pacientes do estudo (49,7%), incluindo 16 pacientes (8,6%) com tais eventos de grau 3 ou 4, e 28 pacientes (15,1%) necessitando de terapia com corticosteroides sistêmicos. Distúrbios da tireoide (20%), erupção cutânea (17,8%), prurido (11,4%) e colite (11,4%) foram os eventos adversos relacionados ao sistema imunológico mais frequentes. Cinco (2,7%) pacientes descontinuaram os inibidores de checkpoint imunológico e 15 (7,0%) foram hospitalizados devido a eventos adversos relacionados ao sistema imunológico. O desenvolvimento de eventos adversos relacionados ao sistema imunológico e inibidores de checkpoint imunológico usados no cenário de primeira linha foram associados a sobrevida livre de progressão prolongada e sobrevida global na análise multivariada. Além disso, idade <75 anos e pontuação ECOG 0 ou 1 foram positivamente associadas à sobrevida global na análise multivariada.

Conclusão: Este estudo baseado em dados brasileiros do “mundo real” confirma o perfil de toxicidade dos inibidores do checkpoint imunológico observado em ensaios clínicos. De acordo com análises retrospectivas anteriores, o desenvolvimento de eventos adversos relacionados ao sistema imunológico foi associado ao resultado de sobrevida do tratamento com inibidores de checkpoint imunológico em pacientes com cânceres sólidos metastáticos.

Keywords:

Brazil - Immunotherapy - Immune checkpoint inhibitors - Toxicity

Descritores:

Brasil - Imunoterapia - Inibidores do checkpoint imunológico - Toxicidade

Publication History

Received: 08 August 2022

Accepted: 23 September 2022

Article published online:
29 December 2022

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