Abstract

Abstract Background: The introduction of immune checkpoint inhibitors such as pembrolizumab has significantly improved the outcomes of patients with metastatic non-small cell lung cancer (NSCLC). Pre-treatment biomarkers and clinical parameters such as body mass index (BMI), neutrophil-lymphocyte ratio (NLR), albumin, and antibiotic exposure have been shown to be prognostic factors in other immunotherapy-treated cancers. Here we report an association between these biomarkers and survival outcomes in metastatic NSCLC patients who received first-line treatment with pembrolizumab-based regimens. Methods: We conducted a retrospective, 3-center study using electronic medical record data for patients with NSCLC treated with first-line pembrolizumab, either as monotherapy or in combination with chemotherapy. Kaplan-Meier analysis was used to describe our primary end-points, progression-free survival (PFS) and overall survival (OS) after initiation of immunotherapy. Log-rank test was used to compare the PFS and OS for antibiotics usage one month prior to therapy initiation. Univariate analysis and Cox proportional modeling were used to analyze pre-treatment BMI, NLR, and albumin relative to PFS and OS. Results: 136 patients were identified in our cohort. 50 (36.8%) patients received pembrolizumab monotherapy, and 86 (63.2%) patients received pembrolizumab with chemotherapy. 95 (69.9%) patients had exposure to antibiotics one month prior to therapy initiation, 40 (29.4%) patients had no exposure, and 1 (0.7%) patient had no reported data on antibiotics usage. Mean NLR was 7.61 (n=135), mean albumin was 3.27 g/dL (n=133), and mean BMI was 25.89 (n=134). On univariate analysis, exposure to antibiotics (log-rank p-value = 0.03), higher NLR (hazard ratio = 1.027; p-value = 0.021), and lower albumin (hazard ratio = 0.385; p-value < 0.001) have significant associations with worse PFS. Furthermore, univariate analysis showed that elevated NLR (hazard ratio = 1.036; p-value = 0.004), lower albumin (hazard ratio = 0.440; p-value = 0.002), and lower BMI (hazard ratio = 0.952; p-value = 0.032) are associated with worse OS. Cox proportional modeling revealed that lower albumin maintains a significant association with worse PFS (hazard ratio = 0.412; p-value<0.001) and worse OS (hazard ratio = 0.509; p-value = 0.004) while considering antibiotic exposure and NLR. Conclusion: Exposure to antibiotics within one month of pembrolizumab initiation, higher baseline NLR, and lower baseline albumin are associated with worse PFS. Elevated baseline NLR, lower baseline albumin, and lower BMI are associated with poorer OS. These results enhance our understanding of how these biomarkers may predict efficacy of immune checkpoint inhibitor therapy in patients with NSCLC. Larger prospective studies should further investigate the clinical utility of these biomarkers. Citation Format: Ishani Joshi, Monica Peravali, Xue Geng, Jiahua Zhang, Giuseppe Giaccone, Chul Kim. Association between pre-treatment biomarkers and survival in metastatic non-small cell lung cancer patients treated with first-line pembrolizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 372.

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