Ravi Salgia, MD, PhD from City of Hope and the AACR 2020 meeting discusses the AACR 2020 abstract entitled Association of molecular characteristics with survival in advanced NSCLC patients treated with checkpoint inhibitors
Objectives: Immune checkpoint inhibitors (ICIs) modified the lung cancer therapy environment. Large proportions of patients however have primary or developed ICI resistance. Molecular characterization is crucial to the selection of patients and to overcoming resistance to inhibitors in checkpoints. This research aims to examine the molecular characteristics associated with ICI outcomes in advanced patients with non-small cell lung cancer ( NSCLC).
Materials and methods: All City of Hope advanced-stage NSCLC patients who obtained ICIs (pembrolizumab, nivolumab, atezolizumab, and durvalumab) were retrospectively identified. Overall survival (OS), pathology and genomic alteration (GA) information including next-generation sequencing ( NGS) data, tumor mutation burden (TMB) and programmed death-ligand 1 (PD-L1) levels were collected from the start of the ICIs. The exact test of Chi-square and Fisher, the Log-rank test is used for demographic comparison, and the survival curves respectively. For survival analysis the univariate and multivariate COX proportional hazard model was used.
Results: It found 346 patients with NSCLC. Univariate and multivariate analyzes find a mixture of OS with PD-L1 level of 50% (hazard ratio [HR], 0.19; 95 % confidence interval [CI], 0.06-0.59; P<0.01), EGFR (HR 7.38; 95 % CI, 1.15-47.42; P<0.05) and TET2 (HR 0.15; 95 % CI, 0.03-0.90; P<0.05). For the 12 patients with genomic alterations (GAs) in TET2 (12/108, 11 percent) versus (vs) 11.5 months in negative TET2 patients (98/108, 89 percent), median OS was not reached [NR]. Interestingly, GAs is mutually exclusive in TET2 and FANCA, and patients with GAs in the FANCA gene (6 percent) had shorter OS (5.5 months vs. 14.5 months, Log-rank test, P<0.05).
Conclusions: We outlined the clinical and molecular characteristics of ICI-treated NSCLC patients. The interaction of GAs in TET2 with longer OS and their reciprocal exclusivity with FANCA GAs was informative in developing new therapeutic strategies for enhancing NSCLC ICI outcomes.
Keywords: lung cancer, molecular sequencing (NGS), inhibitors of the immune control stage, TET2, FANCA, PD-L1, TMB, immunotherapy
Citation Format: Dan Zhao, Isa Mambetsariev, Haiqing Li, Chen Chen, Jeremy Fricke, Patricia Fann, Prakash Kulkarni, Yan Xing, Peter Lee, Andrea Bild, Erminia Massarelli, Marianna Koczywas, Ravi Salgia, Karen Reckamp. Association of molecular properties with survival in advanced non-small cell lung cancer patients treated with [abstract] checkpoint inhibitors. In: Proceedings of the American Cancer Research Association's Annual Meeting 2020; 2020 Apr 27-28 and 22-24 Jun. PA: AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3300.