Chapter 5 174 Introduction The addition of immune checkpoint inhibitors (CPIs) to the armamentarium of medical treatment of advanced non-small cell lung cancer (NSCLC) has increased survival for a minority of patients. Historically, in patients with metastatic disease, 2-year survival rates following platinum-based chemotherapy were 10-20%1. In recent phase III studies, either comparing CPIs alone or CPI-chemotherapy to chemotherapy2, 2-year survival rates in the CPI arms range from 32% to 67%. In addition, long term follow-up of patients treated in early single agent CPI studies indicates that 5-year survival of 15-20% may be expected, even in heavily pretreated patients3,4. At the same time, it is clear that not all patients benefit from treatment with CPIs. Indeed, response rates and survival times can be augmented by pretreatment selection based on tumor characteristics such as PD-(L)1 expression5, staining of CD8 positive cells6, tumor mutational burden (TMB)7 and other genomic markers8,9. The predictive power of the best studied of these, PD-L1 immunohistochemistry, is far from perfect. For example, in previously treated NSCLC patients with PD-L1 staining of at least 50%, the objective response rate (ORR) to pembrolizumab is 44%5. Thus, alternative predictive biomarkers for response and clinical benefit are needed. We sought to develop a serum-based, pretreatment protein test to avoid the need for tissue biopsies, which are typically required to analyze tumor-related biomarkers. Here, we report on the development of such a test in advanced NSCLC treated with single agent CPI in the second-line setting.
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