Evaluation of clinical and safety outcomes of cancer vaccines in patients with advanced non-small cell lung cancer after first-line therapy: a systematic review and meta-analysis.

BACKGROUND

Despite numerous randomized controlled trials (RCTs) on cancer vaccines, systematic evaluations of their efficacy and safety for patients with advanced non-small cell lung cancer (NSCLC) following first-line therapy remain lacking.

METHODS

In this systematic review and meta-analysis (PROSPERO, CRD42024568178), PubMed, Cochrane Library, and Embase databases were searched from inception up to December 27, 2024. Published phase II or III RCTs reporting survival outcomes in advanced or metastatic NSCLC patients who received vaccine therapy after first-line therapy were included. Data were independently extracted by two reviewers. The primary outcome was overall survival (OS), with progression-free survival (PFS) as secondary outcome. Treatment-related adverse events (TRAEs) was the major safety outcome. Random-effects model was employed in this meta-analysis. Risk of bias was evaluated with RoB 2.

FINDINGS

Eleven RCTs comprising 3228 patients (67% male, n = 2162) were included, without high risk of bias. The included studies involved employing cancer vaccines as first-line maintenance therapy, second-line therapy, or third-line therapy. In general, Cancer vaccines associated with improved OS (HR = 0.85, 95% CI, 0.78-0.92, < 0.001) but did not significantly improve PFS (HR = 0.91, 95% CI, 0.79-1.05, = 0.195). Subgroup analyses indicated better OS for patients with ECOG = 1, first-line chemotherapy, squamous cell carcinoma, stable disease after first-line therapy, stage IV, and smoking history. Squamous cell carcinoma (HR = 0.74, 95% CI, 0.61-0.90, = 0.003) responded better to vaccine therapy than adenocarcinoma (HR = 0.83, 95% CI, 0.55-1.26, = 0.377). The pooled OR for TRAEs was 1.5 (95% CI, 0.63-3.61, = 0.361). Exploratory analysis indicated that immune response to cancer vaccines may serve as a predictive biomarker for vaccines effect. Besides, consistent efficacy and safety results were obtained when the meta-analysis was specific to first-line maintenance therapy based on seven trials.

INTERPRETATION

This meta-analysis demonstrated the clinical efficacy and safety of cancer vaccines in advanced NSCLC patients after first-line therapy, especially in those with squamous cell carcinoma. Immune response was identified as a predictive biomarker for vaccines effect. This study provides the state-of-the-art evidence for the clinical application of cancer vaccines in advanced NSCLC patients after first-line therapy.

FUNDING

20240484580, 20230484314, 2023YFF0723500, 2021RU002, 82173386, RZ2022-04.