Efficacy and Safety of Different Treatment Regimens for Previously Untreated Patients with HER2-positive Advanced
Yuqi He1, Qi Kang1, Shanshan Xu1
1The First People's Hospital of Lanzhou City(Second Clinical Medical College of Gansu University of Chinese Medicine), Lanzhou, Gansu Province, China.
Objective:
The development of treatments for advanced gastric cancer (AGC) has made significant advances over the past decade. Although clinical trials for novel drugs targeting HER2-positive AGC are ongoing, current clinical management still faces challenges. Therefore, further comparison of the effectiveness of such combination therapies is needed.
Methods:
comprehensive search was conducted in the PubMed, Embase, and Cochrane databases, with the search cut-off date set to May 2025. Outcomes were evaluated using indicators such as progression-free survival (PFS) and overall survival (OS).
Results:
Our study included only randomized controlled trials comparing combination regimens of targeted and/or immunotherapy, involving 3,231 patients across eight different interventions.The network meta-analysis revealed that no treatment regimen demonstrated a statistically significant improvement in OS or PFS. However, a trend toward improved PFS was observed with HLX22 plus HLX02 and chemotherapy compared to trastuzumab-based chemotherapy, although the difference was not statistically significant (MD=-0.94, 95% CI: -5.26-3.37). Pembrolizumab in combination with trastuzumab and chemotherapy significantly improved the objective response rate (ORR).Cumulative ranking probabilities indicated that trastuzumab plus chemotherapy may be associated with the longest PFS, while chemotherapy alone ranked highest in OS, though all confidence intervals included the null value.
Conclusion:
No first-line regimen significantly improved OS or PFS in HER2-positive advanced gastric cancer. However, HLX22-based and immune-combination strategies show potential clinical value-particularly in enhancing ORR-and merit further investigation.
Insights
No new first-line treatments significantly improved survival for advanced gastric cancer. However, combination therapies, including HLX22 and immunotherapy, show promise for improving objective response rates in HER2-positive patients.
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- Advanced gastric cancer (AGC) treatment has advanced, but challenges remain for HER2-positive cases.
- Novel targeted and immunotherapy agents are under investigation for AGC.
- Further comparative effectiveness research is needed for combination therapies.
Purpose of the Study:
- To compare the effectiveness of various combination therapies for HER2-positive advanced gastric cancer.
- To evaluate outcomes including progression-free survival (PFS) and overall survival (OS).
Main Methods:
- A comprehensive literature search of PubMed, Embase, and Cochrane databases up to May 2025.
- Inclusion of randomized controlled trials (RCTs) comparing targeted and/or immunotherapy combinations.
- Network meta-analysis of eight interventions involving 3,231 patients.
Main Results:
- No treatment regimen demonstrated statistically significant improvement in OS or PFS.
- A trend towards improved PFS was noted with HLX22 plus HLX02 and chemotherapy versus trastuzumab-based chemotherapy (not statistically significant).
- Pembrolizumab combined with trastuzumab and chemotherapy significantly improved objective response rate (ORR).
Conclusions:
- Current first-line regimens do not significantly improve OS or PFS in HER2-positive advanced gastric cancer.
- HLX22-based and immune-combination strategies show potential, particularly in enhancing ORR.
- These novel strategies warrant further investigation in clinical trials.
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