Efficacy of osimertinib in advanced T790M-positive NSCLC after progression to prior EGFR-TKI: real world data from a Brazilian cohort

ABSTRACT

Objectives: Osimertinib is a third-generation EGFR inhibitor with activity against both sensitizing and resistance mutations. Following results of the phase III study, AURA3, which led to the approval of osimertinib worldwide, we have conducted ASTRIS with the aim of confirming the efficacy and safety of osimertinib. Methods: This is a phase IV, international, multicentric, open trial assessing the efficacy and safety of osimertinib at a dose of 80mg daily, orally. Eligible patients were those with diagnosis of T790M-positive NSCLC on progression after prior EGFRTKI. Herein, we present the Brazilian experience at ASTRIS. Results: Eighty-eight patients were enrolled in Brazil between August, 2015 and March, 2017. The median age was 34-89 (years), and most were females (66%). Fiftyfour patients (61%) had received prior therapy with erlotinib, forty-two (48%) with gefitinib, and 3 (3%) with afatinib. Exon 19 deletions were the most common primary mutation in EGFR, present in 55 cases (62.5%), followed by L858R in 24 cases (27%). The response rate was 58.2% (95%CI = 46.6-69.2), and median progression-free survival was 9.4 months (95%CI = 8.2-not reached). The most common AE was pneumonia (5 cases). Only 1 patient (1.1%) had a pneumonitis-like event and 2 patients (2.3%) had a prolongation of the QTc interval. Conclusion: In a realworld setting, osimertinib constitutes a safe and effective therapeutic option for Brazilian patients with advanced T790M-positive NSCLC after progression on a prior EGFR-TKI, including those patients with central nervous system metastasis. Our findings support previous observations and add valuable information regarding osimertinib effectiveness in Brazilian patients.

RESUMO

Objetivos: Osimertinibe é um inibidor de EGFR de terceira geração com atividade contra mutações sensibilizantes e resistentes. Após os resultados do estudo de AURA3, fase III, que levaram à aprovação do osimertinibe em todo o mundo, conduzimos o ASTRIS com o objetivo de confirmar a eficácia e a segurança do osimertinibe. Métodos: Trata-se de um estudo aberto, de fase IV, internacional, multicêntrico, que avalia a eficácia e a segurança do osimertinibe na dose de 80mg por dia, por via oral. Os pacientes elegíveis foram aqueles com diagnóstico de CPNPC T790M-positivo, em progressão após EGFR-TKI prévia. Aqui, apresentamos a experiência brasileira no ASTRIS. Resultados: Oitenta e oito pacientes foram matriculados no Brasil, entre agosto de 2015 e março de 2017. A idade média foi de 34-89 anos e a maioria era do sexo feminino (66%). Cinquenta e quatro pacientes (61%) haviam recebido terapia prévia com erlotinibe, quarenta e dois (48%) com gefininibe e 3 (3%) com afatinibe. As deleções do exão 19 foram as mutações primárias mais comuns no EGFR, presente em 55 casos (62,5%), seguida por L858R em 24 casos (27%). A taxa de resposta foi de 58,2% (IC95% = 46,6-69,2) e a sobrevida média livre de progressão foi de 9,4 meses (IC95% = 8,2 - não atingido). O EA mais comum foi pneumonia (5 casos). Apenas 1 paciente (1,1%) teve um evento semelhante à pneumonite e 2 pacientes (2,3%) prolongaram o intervalo QTc. Conclusão: Em um cenário do mundo real, o osimertinibe constitui uma opção terapêutica segura e eficaz para pacientes brasileiros com CPNPC T790M-positivo avançado em progressão após EGFR-TKI prévia, incluindo aqueles com metástase no sistema nervoso central. Nossos resultados apoiam observações anteriores e acrescentam informações valiosas sobre a eficácia de osimertinibe em pacientes brasileiros.

Keywords:

Lung neoplasms - Genes - erbB-1 - Molecular targeted therapy

Descritores:

Neoplasias pulmonares - Genes erbB-1 - Terapia direcionada molecular

Financial support: none to declare.

Publication History

Received: 21 February 2020

Accepted: 28 February 2020

Article published online:
21 May 2020

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