Clinical Oncology: Case Reports.

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Remarkable Effect of Atezolizumab in Advanced Non-Small Cell Lung Cancer with PD-L1 Negative but Genome Instability is Increased: Case Report

Immune checkpoint inhibitors have become important paradigms for treating non-small cell lung cancer patients. Although several biomarkers indicating the efficacy of immune checkpoint inhibitors have been reported, these markers sometimes are not accurate concerning the therapeutic effect. A 63-year-old man without a smoking history was diagnosed with lung adenocarcinoma pathological stage IVB without an epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation, rearrangement of ROS1, or expression of programmed deathligand 1 (PD-L1). Although cytotoxic anticancer therapies were administered, carcinoembryonic antigen (CEA) gradually became elevated, and the lesions progressed. Atezolizumab was administered as third-line chemotherapy, after which CEA normalized. After atezolizumab therapy was started, the Tumor Mutation Burden (TMB) and Microsatellite Instability (MSI) were analyzed in this patient’s samples. The TMB was identified at 16.1 mutations per megabase by next-generation sequencing. MSI was analyzed by a Bethesda panel assay, and three microsatellite loci (D2S123, D5S346, D17S250) were positive. Therefore, this patient was defined as TMB-high and MSI-high (MSI-H).Although this patient had negative PD-L1 expression, atezolizumab showed remarkable efficacy. PD-L1, TMB, and MSI are considered new predictive biomarkers for selecting patients that benefit from immune checkpoint inhibitors. 

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