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Meta-Analysis
. 2024 Apr 1;7(4):e246837.
doi: 10.1001/jamanetworkopen.2024.6837.

Neoadjuvant Chemo-Immunotherapy for Early-Stage Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Giuseppe Luigi Banna  1   2 , Mona Ali Hassan  1 , Alessio Signori  3 , Emilio Francesco Giunta  4 , Akash Maniam  1 , Shobana Anpalakhan  5 , Shyamika Acharige  1 , Aruni Ghose  6 , Alfredo Addeo  7
Affiliations
Meta-Analysis

Neoadjuvant Chemo-Immunotherapy for Early-Stage Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Giuseppe Luigi Banna et al. JAMA Netw Open. .

Abstract

Importance: Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data.

Objective: To assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors.

Data sources: Full-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023.

Study selection: Phase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included.

Data extraction and synthesis: Data extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.

Main outcomes and measures: Two-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated.

Results: Eight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005).

Conclusions and relevance: In this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Banna reported receiving personal fees from Astellas, AstraZeneca, and Amgen outside the submitted work. Dr Giunta reported receiving travel grants from Janssen-Cilag and Bayer and personal fees from Novartis outside the submitted work. Dr Anpalakhan reported receiving conference travel fees and accommodation from Astellas outside the submitted work. Dr Addeo reported receiving personal fees from BMS, Roche, Pfizer, Amgen, AstraZeneca, Astellas, and Eli Lilly & Company for serving on advisory boards and from MSD and Merck for serving on speaker bureaus outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Outcomes by Meta-Analysis
Random-effects restricted maximum likelihood model. EFS indicates event-free survival; HR hazard ratio; RR, relative risk.
Figure 2.
Figure 2.. Subgroup Meta-Analysis of 2-Year Event-Free Survival
Random-effects restricted maximum likelihood model. HR indicates hazard ratio; PD-L1, programmed cell death ligand 1.
Figure 3.
Figure 3.. Subgroup Meta-Analysis of 2-Year Event-Free Survival (EFS) and Pathologic Complete Response by Adjuvant Immune Checkpoint Inhibitor (ICI) and Neoadjuvant ICI-Chemotherapy
Random-effects restricted maximum likelihood model. HR indicates hazard ratio; IT, immunotherapy; RR, relative risk.
See this image and copyright information in PMC

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