Background:

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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.

Objective:

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To evaluate the efficacy and safety of EGFR-TKIs monotherapy

versus

EGFR-TKIs combined with classical Chinese herb formulas in the treatment of NSCLC.

Methods:

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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).

Resuts:

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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).

Conclusions:

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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)