Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis

Abstract

Objective: Atezolizumab is becoming a significant therapy for non-small cell lung cancer (NSCLC), but its efficacy needs to be further improved. The aims of this study are to clarify the potency of atezolizumab-based therapy in advanced NSCLC patients with different clinical and molecular features, and to choose a better therapeutic regimen of atezolizumab to achieve more precise treatment in immunotherapy.

Methods: Randomized clinical trials (RCTs) in the Cochrane Library, PubMed, Embase Science Direct, and Google Scholar, together with major oncology conferences that compared atezolizumab with chemotherapy-based treatment for individuals with advanced NSCLC published prior to February 2022, were searched. Studies, bias risk assessment, and data extraction were selected by two independent authors. We extracted the basic features of the included studies, together with the 95% confidence interval (CI) and hazard ratios (HRs), from all patients and subgroups. The combined treatment data were assessed using the inverse variance weighting method.

Results: Seven RCTs including 4,859 patients were included. Our meta-analysis findings indicated that atezolizumab substantially enhanced OS (HR 0.82; 95% CI, 0.77-0.88; p < 0.00001) and PFS (HR 0.72; 95% CI, 0.61-0.85; p < 0.0001) in patients with advanced NSCLC compared with chemotherapy-based treatment. Atezolizumab substantially enhanced OS in patients aged <65 years old and 65-74 years old, those with wild-type EGFR, those without liver metastases, active or previous smokers, white patients and those with TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3, and TC0 and IC0, but not in patients aged ≥75 years, never smokers, those with liver metastases, those with EGFR mutant, Asians, Black or African Americans, or those with TC1/2 or IC1/2. Patients with advanced NSCLC who received atezolizumab showed OS improvement regardless of sex (male or female), histological type (non-squamous or squamous NSCLC), performance status (0 or 1), and line of treatment (1st-line therapy or ≥2nd-line therapy). Subgroup analysis revealed that male individuals, those with non-squamous NSCLC, those with PS 1, active or previous smokers, and those with wild-type EGFR, TC3 or IC3, and TC1/2/3 or IC1/2/3 achieved OS benefit from atezolizumab treatment not related to the treatment line and treatment regimen.

Conclusions: Age group, smoking history, liver metastasis status, EGFR mutation status, race, and PD-L1 expression can be used to predict the potency of atezolizumab and provide a better treatment regimen for patients with advanced NSCLC to achieve accurate and personalized treatment.

Keywords: atezolizumab; meta-analysis; non-small cell lung cancer; potency; predictor.

Figure 1

PRISMA flow diagram.

Figure 2

Risk of bias graph.

Figure 3

Forest plots of HRs comparing (A) OS and (B) PFS between atezolizumab-based therapy and chemotherapy-based therapy, (C) OS and (D) PFS based on atezolizumab monotherapy, and (E) OS and (F) PFS based on atezolizumab combined therapy.

Figure 4

Forest plots of HRs comparing OS between atezolizumab-based therapy and chemotherapy-based therapy with respect to (A) age group, (B) gender, (C) histological type, (D) PS score, (E) smoking status, (F) liver metastases status, (G) EGFR mutation status, (H) race, (I) PD-L1expression, and (J) treatment line.