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Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A
Wenjie Liu1, Gengwei Huo1,2, Peng Chen1
1Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
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.
Insights
Atezolizumab significantly improves overall survival (OS) and progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC). Patient factors like age, smoking history, and EGFR status predict treatment response, guiding personalized immunotherapy.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Atezolizumab is a key immunotherapy for non-small cell lung cancer (NSCLC).
- Further improvement in atezolizumab efficacy is needed for advanced NSCLC patients.
- Personalized treatment strategies are crucial for optimizing immunotherapy outcomes.
Purpose of the Study:
- To evaluate the effectiveness of atezolizumab-based therapy in advanced NSCLC patients.
- To identify clinical and molecular features influencing atezolizumab response.
- To guide the selection of optimal atezolizumab treatment regimens for precise immunotherapy.
Main Methods:
- A systematic review and meta-analysis of randomized clinical trials (RCTs) comparing atezolizumab with chemotherapy.
- Searches conducted in major databases (Cochrane, PubMed, Embase, Google Scholar) and oncology conferences up to February 2022.
- Data extraction and bias risk assessment performed by two independent authors, with combined treatment data analyzed using inverse variance weighting.
Main Results:
- Seven RCTs with 4,859 patients were included. Atezolizumab significantly improved overall survival (OS) (HR 0.82) and progression-free survival (PFS) (HR 0.72) compared to chemotherapy.
- OS benefits were observed in specific subgroups: younger patients (<75 years), wild-type EGFR, no liver metastases, active/previous smokers, white patients, and those with specific PD-L1 expression levels (TC3/IC3, TC2/3/IC2/3, TC1/2/3/IC1/2/3, TC0/IC0).
- No significant OS benefit was seen in patients aged ≥75 years, never smokers, those with liver metastases, EGFR mutant, Asians, Black/African Americans, or those with TC1/2/IC1/2. Benefits were consistent across sex, histology, performance status, and treatment lines.
Conclusions:
- Patient characteristics including age, smoking history, liver metastasis status, EGFR mutation status, race, and PD-L1 expression are predictive of atezolizumab efficacy.
- These factors can inform the development of personalized treatment regimens for advanced NSCLC.
- Optimizing atezolizumab therapy based on individual patient profiles can lead to more precise and effective immunotherapy.
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