2023 World Conference on Lung Cancer (Posters)-EP13.05. Temozolomide-associated Hypermutation and Response to Immunotherapy in Advanced Pulmonary Neuroendocrine Tumors.

EP13.05. Temozolomide-associated Hypermutation and Response to Immunotherapy in Advanced Pulmonary Neuroendocrine Tumors. - PDF(Slides)

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In this study, the researchers investigated the response to immunotherapy in advanced pulmonary neuroendocrine tumors (PNET) that were treated with temozolomide (TEM). They found that one out of five patients showed temozolomide-associated hypermutation, which is characterized by a marked increase in tumor mutational burden (TMB) and resistance to temozolomide-induced cytotoxicity. The patient with temozolomide-associated hypermutation was treated with pembrolizumab and had stable disease as the best response.<br /><br />The study included five patients with atypical carcinoids who underwent whole genome sequencing (WGS). Four patients did not show the enrichment of a specific mutation pattern, while one patient showed temozolomide-associated hypermutation. This patient had a methylated MGMT promoter, a very high tumor mutational load, and a PD-L1 expression of 5%. The patient was treated with pembrolizumab and has been continuing treatment for five months.<br /><br />The researchers concluded that temozolomide-associated hypermutation occurs in a subset of patients with advanced PNET and may have potential implications for immunotherapy response. However, the effect of pembrolizumab in this patient population was modest. The series of patients will be expanded to better understand the occurrence of temozolomide-associated hypermutation and the potential benefits of checkpoint inhibition in pulmonary neuroendocrine tumors.<br /><br />Overall, this study highlights the potential role of temozolomide-associated hypermutation in predicting response to immunotherapy in patients with advanced PNET. Further research is needed to better understand the mechanisms and implications of this hypermutation and to optimize treatment strategies for patients with PNET.

Asset Subtitle

Wieneke Buikhuisen

Meta Tag

Speaker Wieneke Buikhuisen

Topic SCLC & Neuroendocrine Tumors: NETs

Keywords

immunotherapy

pulmonary neuroendocrine tumors

temozolomide

temozolomide-associated hypermutation

tumor mutational burden

cytotoxicity

pembrolizumab

atypical carcinoids

whole genome sequencing

checkpoint inhibition