Direct Comparison Between the Addition of Pembrolizumab or Bevacizumab for Chemotherapy-Based First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer Lacking Driver Mutations.

Jiatao Liao,Jialei Wang,Hui Yu,Chang Liu,Xianghua Wu,Qianqian Long,Xinmin Zhao,Si Sun,Yao Zhang,Ying Lin,Huijie Wang

doi:10.3389/fonc.2021.752545

Abstract

BackgroundThe addition of bevacizumab or pembrolizumab to pemetrexed-platinum chemotherapy has produced significant clinical benefits to patients with untreated, advanced non-squamous non-small cell lung cancer (NSCLC) lacking targetable genetic aberrations. However, the direct comparison between these two first-line treatments needs to be investigated.MethodsWe retrospectively investigated the medical records of 102 patients with stage IIIB~IV non-squamous NSCLC, and without sensitizing EGFR/ALK/ROS1 alterations. All patients received pembrolizumab or bevacizumab plus pemetrexed-platinum chemotherapy as the first-line treatment between December 2018 to April 2021 at Fudan University Shanghai Cancer Center. Assessments included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). We also evaluated the prognostic biomarkers in the overall population and explored potential predictive biomarkers to aid the selection of optimal treatment regimens.ResultsThe median PFS was 10.0 months in the pembrolizumab group and 9.2 months in bevacizumab group (HR = 1.006; P = 0.982), while the median OS was not reached in either group (HR= 1.193; P =0.714). ORR was 36.7% versus 43.4% (P = 0.548) and DCR was 89.8% versus 92.5% (P = 0.735) in the pembrolizumab and bevacizumab groups, respectively. In the overall study population, baseline lymphocyte to monocyte ratio (LMR) >1.95 (HR = 0.312, P < 0.001) was an indicator of longer PFS. The presence of baseline bone metastasis (HR = 4.107, P = 0.009), baseline lactate dehydrogenase (LDH) >300 U/L (HR = 4.300, P = 0.025) and LMR ≤1.95 (HR = 5.291, P = 0.039) were associated with inferior OS. Baseline neutrophil-to-lymphocyte ratio (NLR) ≤3.10 was predictive of significantly favorable OS in the bevacizumab combination treatment (HR = 5.073, P = 0.039). The safety profiles were generally comparable between the two groups.ConclusionsIn patients with chemotherapy-naive, advanced, non-squamous NSCLC who lack driver mutations, the efficacy and safety of pembrolizumab and bevacizumab when combined with pemetrexed-platinum were comparable. For patients with baseline NLR ≤3.10, the bevacizumab combination therapy elicited significantly better OS benefits.

Highlights

Despite the benefits of obtaining early diagnoses and interventions, approximately 57% of lung cancer patients are not diagnosed until the presence of metastatic disease
In the final analysis of the large, open-label, phase III IMpower150 study [19, 20], numerically but not statistically significant overall survival (OS) improvement was shown in atezolizumab -carboplatin-paclitaxel treatment compared with bevacizumab-carboplatin-paclitaxel treatment for metastatic non-squamous non-small cell lung cancer (NSCLC) patients, regardless of programmed death-ligand 1 (PD-L1) level, EGFR/ALK genetic alterations or baseline liver metastasis status
Consistent with the corresponding results in the IMpower150 study, the results of the current study found that the addition of pembrolizumab or bevacizumab to first-line standard chemotherapy generally conferred similar levels of clinical outcome improvements to patients

Summary

Introduction

Despite the benefits of obtaining early diagnoses and interventions, approximately 57% of lung cancer patients are not diagnosed until the presence of metastatic disease. According to the KEYNOTE-189 trial, pembrolizumab plus pemetrexed and platinum has manifested significantly improved median progression-free survival (PFS, 9.0 vs 4.9 months; hazard ratio [HR] = 0.49) and median OS (22.0 vs 10.6 months; HR = 0.56) with manageable toxicity in untreated, metastatic non-squamous NSCLC patients without targetable mutations [9]. Despite their benefits to patients, it is still elusive about the selection criteria between bevacizumab and pembrolizumab. The direct comparison between these two first-line treatments needs to be investigated

Methods

Results

Conclusion