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Neoadjuvant and Adjuvant Immunotherapy: Opening New Horizons for Patients With Early-Stage Non-small Cell Lung Cancer.

ABSTRACT: Lung cancer is the most common malignant tumor with the highest mortality, and about 84% are non-small cell lung cancer (NSCLC). However, only a small proportion of patients with newly diagnosed lung tumors can receive curative surgery and have a high risk of postoperative recurrence. At present, there are many perioperative treatment methods being continuously explored, such as chemotherapy and targeted therapy, continuously enriching the content of neoadjuvant and adjuvant therapy in early-stage NSCLC. But disappointingly, for patients with driver gene mutation, the significant disease-free survival (DFS) benefit of targeted drugs failed to translate into overall survival (OS) benefit, and for negative patients, chemotherapy has reached a plateau in improving efficacy and survival. Immunotherapy represented by immune checkpoint inhibitors (ICIs) has been researched in more and more clinical trials in patients with early-stage operable disease, gradually enriching the existing treatments. This review focuses on the research progress of clinical trials of neoadjuvant and adjuvant therapy with ICIs in early-stage NSCLC, the exploration of response evaluation and predictive biomarkers, and the urgent problems to be solved in the future.

SUBMITTER: Bai R

PROVIDER: S-EPMC7581706 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Neoadjuvant and Adjuvant Immunotherapy: Opening New Horizons for Patients With Early-Stage Non-small Cell Lung Cancer.

Bai Rilan R Li Lingyu L Chen Xiao X Chen Naifei N Song Wei W Cui Jiuwei J

Frontiers in oncology 20201009

Lung cancer is the most common malignant tumor with the highest mortality, and about 84% are non-small cell lung cancer (NSCLC). However, only a small proportion of patients with newly diagnosed lung tumors can receive curative surgery and have a high risk of postoperative recurrence. At present, there are many perioperative treatment methods being continuously explored, such as chemotherapy and targeted therapy, continuously enriching the content of neoadjuvant and adjuvant therapy in early-sta ...[more]

PMID: 33163406

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Project description:ImportanceRandomized 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.ObjectiveTo 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 sourcesFull-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 selectionPhase 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 synthesisData 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 measuresTwo-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.ResultsEight 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 relevanceIn 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.

Dataset Information

Neoadjuvant and Adjuvant Immunotherapy: Opening New Horizons for Patients With Early-Stage Non-small Cell Lung Cancer.

Publications

Neoadjuvant and Adjuvant Immunotherapy: Opening New Horizons for Patients With Early-Stage Non-small Cell Lung Cancer.

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