Association of High Neutrophil-to-Lymphocyte Ratio With Poor Outcomes of Pembrolizumab Therapy in High-PD-L1-expressing Non-small Cell Lung Cancer

Abstract

Background: This study aimed to determine whether the neutrophil-to-lymphocyte ratio (NLR) reflected poor treatment benefits in patients with tumor proportion score (TPS) ≥50% and who under went first-line pembrolizumab monotherapy. Patients and Methods: This study retrospectively analyzed patients with untreated stage III/IV or recurrent non-small cell lung cancer (NSCLC) with TPS ≥50% and who received pembrolizumab monotherapy at two hospitals between February 2017 and April 2019. The NLR was calculated from pre-treatment complete blood counts. Results: A total of 51 previously untreated patients with NSCLC who had TPS ≥50% and who underwent pembrolizumab monotherapy were evaluated. Multivariate analysis revealed that high NLR, Eastern Cooperative Oncology Group performance status (PS) ≥2, stage IV or recurrent cancer, and TPS=50−74% were significantly and independently associated with poor progression-free survival. Moreover, high NLR and PS ≥2 were significantly associated with short overall survival. Conclusion: A high pre-treatment NLR was associated with significantly short progression-free and overall survival in previously untreated patients with NSCLC with high expression of programmed cell-death ligand 1 treated with pembrolizumab monotherapy.Lung cancer remains the leading cause of cancer-related death worldwide (1) despite dramatic advances in cutting edge and radical treatments, including targeted therapies for advanced non-small cell lung cancer (NSCLC). Targeted therapies have improved the survival of patients with driver oncogenes and are standard first-line therapies. However, for patients without driver oncogenes, improvements in survival were minimal until immunotherapeutic alternatives became available.Therapeutic agents such as nivolumab, pembrolizumab, and atezolizumab, which are antibodies that target programmed death 1 (PD1) or its ligand (PD-L1), have significantly improved survival compared with docetaxel as a second-line treatment for advanced NSCLC without any selection or with a PD-L1 tumor proportion score (TPS) of ≥1% (2-5). However, in studies with the aforementioned results, the objective response was low at 15%, indicating that only few patients benefited from the treatment, warranting the need for precise patient selection and additional efficacy studies. Selection of patients based on PD-L1 expression in tumor tissue is perhaps the best biomarker for treating advanced NSCLC with anti-PD1/L1 antibody. Two phase III studies compared pembrolizumab monotherapy with platinum-based chemotherapy as the firstline treatment in patients with untreated NSCLC who had TPS ≥50% [KEYNOTE-024 (6)] and >1% [KEYNOTE-042 (7)]. Pembrolizumab monotherapy significantly prolonged overall survival (OS) and progression-free survival (PFS) and has become a standard, first-line treatment. However, in KEYNOTE-042 (7), the PFS and OS curves of patients with TPS ≥50% suggested that certain patients were unlikely to benefit from pembrolizumab monotherapy. The KEYNOTE-189 and KEYNOTE-407 studies (8) revealed...

Pretreatment Neutrophil-to-Lymphocyte Ratio (NLR) May Predict the Outcomes of Advanced Non-small-cell Lung Cancer (NSCLC) Patients Treated With Immune Checkpoint Inhibitors (ICIs)

“…We summarized the characteristics in Table 1. Of all included studies, five were performed in the United States (7,31,33,34,40), four in Japan (32,36,39,44), and the remaining eight studies were conducted in Switzerland (35), Canada (37), France (38,45), Bulgaria (41), China (42), Germany (43), and Italy (46), respectively. In terms of the ICIs used, 11 studies reported on nivolumab (7, 31-36, 39, 42, 45, 46), 2 studies reported on pembrolizumab (41,44), and the remaining 4 studies did not specify the type of ICIs (37,38,40,43).…”

Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Location in Patients With EGFR Mutant Metastatic Non-Small Cell Lung Cancer Treated with TKIs

“…As the NLR as in ammatory marker is playing more and more in uential role, it is widely analyzed in the solid tumor, such as ovarian cancer, urothelial carcinoma, head and neck cancer, lung cancer, hepatocellular carcinoma and so on 13 . The majority of the analysis focus on the multiple comprehensive treatments, including chemotherapy, chemoradiotherapy, radiation therapy, surgery, immunotherapy and immunotherapy combined radiotherapy [14][15][16][17][18][19][20] . The mechanism re ects the patients' in ammatory and systemic immune status.…”

Prognostic value of the neutrophil-to-lymphocyte ratio and primary tumor location in patients with EGFR-mutated metastatic non-small cell lung cancer treated with TKIsNote: We found that we got a wrong results in the previous article. So, we checked our collected database and calculated again and corrected now.

“…As the NLR as an in ammatory marker plays an increasingly role, it is widely analyzed in the solid tumors, such as ovarian cancer, urothelial carcinoma, head and neck cancer, lung cancer, hepatocellular carcinoma and so on [16]. The majority of the analyses focus on the multiple comprehensive treatments, including chemotherapy, chemoradiotherapy, radiation therapy, surgery, immunotherapy and immunotherapy combined with radiotherapy [13,[17][18][19][20][21][22]. The mechanism re ects the patients' in ammatory and systemic immune status.…”