Pembrolizumab and Chemotherapy Combination Prolonged Progression-Free Survival in Patients with NSCLC with High PD-L1 Expression and Low Neutrophil-to-Lymphocyte Ratio

Abstract

The use of immune checkpoint inhibitors (ICIs) has provided overall survival (OS) benefits in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, studies comparing ICIs monotherapy with combination therapy either with chemotherapy or radiotherapy in programmed death-ligand 1 high expressors remain limited. This study aimed to retrospectively compare the treatment efficacy of the therapies by studying 47 patients with treatment-naïve advanced NSCLC who received ICI monotherapy (n = 28) or combination therapy either with chemotherapy or radiotherapy (n = 19). Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method and compared using log–rank tests. It was observed that patients who received combination therapy had a better PFS than monotherapy, but no such significant benefit was observed in OS. The difference in PFS was higher in the subgroup of patients with low neutrophil-to-lymphocyte ratio (NLR) than in the high-NLR patient subgroup. This study suggests that pembrolizumab in combination with chemotherapy or radiotherapy could provide a significant benefit in PFS, especially in patients with treatment-naïve advanced NSCLC with low NLR. Furthermore, our study also demonstrates the potential use of NLR as a biomarker for prediction of treatment outcomes in patients with advanced NSCLC receiving combination therapy.

Low neutrophil-to-lymphocyte ratio predicts overall survival benefit in advanced NSCLC patients with low PD-L1 expression and receiving chemoimmunotherapy

“…This allowed us to compare the effectiveness of chemotherapy and immunotherapy in each subgroup. In our previous study, which enrolled patients with high PD-L1 expression, a low NLR was found to predict improved PFS in patients receiving a combination of chemotherapy and pembrolizumab compared to those receiving pembrolizumab monotherapy ( 15 ). In this study, we further established that patients with a low NLR significantly benefited from improved PFS and OS when undergoing chemoimmunotherapy compared to chemotherapy alone.…”

“…However, no study has yet focused on the predictive role of NLR. Recently, we also established that a low NLR could predict the progression-free survival (PFS) benefit in NSCLC patients with high PD-L1 expression who received combination therapy compared to those receiving only ICIs ( 15 ). We hypothesized that NLR could also be a predictive biomarker for NSCLC patients with PD-L1 expression below 50%.…”

Impact of primary resistance to front-line targeted therapy in metastatic renal cell carcinoma on subsequent immune-checkpoint-inhibition

“…NLR as an easily measurable biomarker demonstrated to predict outcome in various cancers. Although a higher NLR was associated with poorer outcomes, there is no validated cut-off value distinguishing high from low, and therefore varies in literature [17,[24][25][26]. Recently Pham et al demonstrated a poorer OS for NLR ≥ 3 in 36 aRCC patients receiving ICI.…”

Immune escape mechanism of PD-1/PD-L1 in non-small-cell lung cancer(NSCLC) and its related drug treatment

“…Although platinum + paclitaxel + pembrolizumab could prolong PFS, the median TFS was almost the same, and the incidence of severe TRAEs withdrawal was higher than that of chemotherapy alone. Therefore, the appropriate group of patients receiving combination therapy should be carefully selected [4].…”