Feasibility and Safety of PD-1/L1 Inhibitors for Non-Small Cell Lung Cancer in Front-Line Treatment

A Bayesian Network Meta-Analysis

Hengrui Liang; Guo Lin; Wei Wang; Jun Huang; Yilin Yang; Yuting Lan; Runchen Wang; Fei Cui; Zhexue Hao; Hongsheng Deng; Shen Zhao; Bo Cheng; Shan Xiong; Jianfu Li; Caichen Li; Jun Liu; Jianxing He; Wenhua Liang

Disclosures

Transl Lung Cancer Res. 2020;9(2):188-203. 

In This Article

Abstract and Introduction

Abstract

Background: This Bayesian network meta-analysis (NMA) was conducted to compare efficacy and safety of programmed death 1/ligand 1 (PD-1/L1) inhibitors in previous untreated advanced non-small cell lung cancer (NSCLC) patients.

Methods: Eligible studies evaluating first-line anti-PD-1/L1 based regimens in advanced NSCLC patients were included. Overall survival (OS), progression free survival (PFS), objective response rate (ORR), as well as treatment-related severe adverse events (tr-SAE) were synthesized within the Bayesian framework. Subgroup analysis was conducted according to PD-L1 expression.

Results: Twelve studies including 7,490 patients and 9 treatment strategies were enrolled in this study. For the PD-L1 expression non-selective patients, all chemo-immunotherapies were significantly better than chemotherapy for prolonging OS and PFS, except for caremlizumab plus chemotherapy (HR =0.72) failed to show advantages for OS. In addition, pembrolizumab plus chemotherapy showed better PFS than nivolumab plus ipilimumab (HR =0.66). In PD-L1 ≥50% patients, all immunotherapy was better than chemotherapy for OS, except for nivolumab (HR =0.83) and nivolumab plus ipilimumab (HR =0.70). For PFS, pembrolizumab plus chemotherapy (HR =0.39), atezolizumab plus chemotherapy (HR =0.47) and pembrolizumab (HR =0.67) were significantly better than chemotherapy. In PD-L1 1–49% patients, pembrolizumab plus chemotherapy (HR =0.52) and atezolizumab plus chemotherapy (HR =0.70) were better than chemotherapy for PFS. In the PD-L1 positive or negative group, all included corresponding regimens were equivalence according to OS and PFS.

Conclusions: We conducted a systematic comparison of first line immunotherapy for advanced NSCLC. Chemo-immunotherapies were better than chemotherapy and mono-immunotherapies in most patients. Pembrolizumab might have better efficacy than other PD-1/L1 inhibitors.

Introduction

Non-small cell lung cancer (NSCLC) occupies 85% of all lung cancer cases.[1] The majority of NSCLC patients are diagnosed at advanced stage and the prognosis for these patients is poor, therefore systematic therapy is the primary choice. Nearly 30–40% NSCLC patients owned sensitive mutations, that may suitable for corresponding tyrosine kinase inhibitors. However, effective treatments for other patients without mutations are rather limited. The response rate of traditional chemotherapy is only 15–30%.[2]

Programmed death 1/anti-programmed death ligand 1 (PD-1/L1) as an inhibitory pathway detected in various malignant tumors that regulates the function of autoimmunity to against tumors, therefore the inhibitors of PD-1/L1 pathway started a new era of cancer treatment.[3,4] Except for FDA approved PD-1/L1 inhibitors in NSCLC (nivolumab, pembrolizumab, atezolizumab and durvalumab), many other agents with ongoing clinical trials also demonstrated satisfactory efficacy and safety for advanced NSCLC.

Recently, a series of randomized controlled trials (RCTs) demonstrated significant clinical benefits in front line treatment for NSCLC using PD-1/L1 inhibitors, including longer time-to-event outcomes and less side effects.[5–7] However, no head-to-head clinical trial has ever compared which PD-1/L1 agent or strategy is the optimal choice. In addition, there is no study comparing the efficacy of PD-1/L1 inhibitors according to PD-L1 expression.

To address this gap, we performed a Bayesian network meta-analysis (NMA) of RCTs to compare these strategies for untreated advanced NSCLC, attempting to identify the optimal treatment.

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