Efficacy and Safety of Different Types of Traditional Chinese Medicine Preparations Combined with EGFR-TKIs for Patients with Non-Small Cell Lung Cancer: A Network Meta-analysis

Lung cancer remains one of the most malignant cancers worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are recommended as first-line treatments for advanced EGFR-mutated NSCLC. Classical Chinese herb formulas have shown potential clinical benefits in NSCLC management. However, few studies have systematically compared the efficacy and safety of EGFR-TKIs monotherapy versus EGFR-TKIs combined with classical Chinese herb formulas.

To evaluate the efficacy and safety of EGFR-TKIs monotherapy versus EGFR-TKIs combined with classical Chinese herb formulas in the treatment of NSCLC.

A systematic search was conducted to identify randomized controlled trials (RCTs) in which patients with NSCLC were randomly assigned to receive either EGFR-TKIs monotherapy or EGFR-TKIs combined with classical Chinese herbal formulas. The combined regimens include EGFR-TKIs plus Chinese herbal compounds (CHCT), EGFR-TKIs plus Chinese traditional medicine injections (CTMIT), and EGFR-TKIs plus Chinese patent medicines (CPMT). Electronic databases search included PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Data, VIP Database, the International Clinical Trial Registry Platform, and the Chinese Clinical Trial Registry, from inception updated to February 26, 2025. Given that all outcomes were binary, odds ratios (ORs) along with 95% confidence intervals (CIs) were computed. Pairwise comparisons and Bayesian network meta-analyses were used for the same outcome assessment, including progressive disease (PD), disease control rate (DCR), objective response rate (ORR), rash, diarrhea, and drug-induced liver injury (DILI) with the former reporting ORs and 95% CIs while the latter ORs and 95% credible intervals (CrIs).

A total of 155 RCTs involving 12,441 patients with NSCLC were included. For efficacy outcomes, EGFR-TKIs monotherapy was associated with a higher risk of PD compared with CHCT (OR: 2.43, 95% CrI: 2.11-2.76), CTMIT (OR: 2.98, 95% CrI: 2.47-3.58), and CPMT (OR: 1.94, 95% CrI: 1.44-2.64) combination therapies, while CPMT was associated with a lower risk of PD than CTMIT (OR: 0.65, 95% CrI: 0.46-0.94). In terms of ORR, CHCT (OR: 0.53, 95% CrI: 0.47-0.59), CTMIT (OR: 0.43, 95% CrI: 0.36-0.50), and CPMT (OR: 0.52, 95% CrI: 0.40-0.68) combination therapies all demonstrated significantly higher ORR than EGFR-TKIs monotherapy, with CTMIT also showing a higher ORR compared with CHCT (OR: 0.81, 95% CrI: 0.67-0.99). For DCR, combination therapy with CHCT (OR: 0.39, 95% CrI: 0.34-0.46), CTMIT (OR: 0.33, 95% CrI: 0.26-0.42), and CPMT (OR: 0.57, 95% CrI: 0.41-0.77) combination therapies were superior to EGFR-TKIs monotherapy, and both CHCT (OR: 1.44, 95% CrI: 1.01-2.05) and CTMIT (OR: 1.70, 95% CrI: 1.16-2.50) showed better DCR than CPMT. For safety outcomes, EGFR-TKIs monotherapy was associated with a higher incidence of rash compared with CHCT (OR: 1.82, 95% CrI: 1.46-2.30) and CTMIT (OR: 1.55, 95% CrI: 1.01-2.41) combination therapies, a higher incidence of diarrhea compared with CHCT (OR: 2.52, 95% CrI: 1.99-3.21) and CPMT (OR: 2.56, 95% CrI: 1.43-4.58), and a higher incidence of DILI compared with CHCT (OR: 2.02, 95% CrI: 1.33-3.13).

This study provides evidence to support the potential value of combining Chinese herbal formulas with EGFR-TKIs in the treatment of NSCLC, aligning with current clinical guidelines. The findings indicate that EGFR-TKIs combined with Chinese herbal formulas (CHCT, CTMIT, CPMT) are associated with higher ORR and DCR, and a lower risk of PD, compared with EGFR-TKIs monotherapy. Additionally, CHCT may reduce the incidence of rash in EGFR-TKIs treated patients. Further well-designed RCTs are warranted to compare the efficacy and safety of different combined therapeutic strategies in NSCLC patients. (Registration No. CRD42024521654).