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Anti-Human Epidermal Growth Factor Receptor-2 Therapies in Biliary Tract Cancers: A Meta-Analysis on Disease
Silvia Camera1, Margherita Rimini1, Silvia Foti1
1Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy.
Introduction:
In recent years, the therapeutic scenario of metastatic biliary tract cancers (BTCs) beyond first-line has profoundly changed owing to target therapies. human epidermal growth factor receptor-2 (HER2) represents a promising molecular target that is frequently altered in BTC. The present meta-analyses aimed to describe the response rates and survival outcomes in patients with HER2-positive locally advanced/metastatic BTC treated with anti-HER2 therapies. Moreover, the study is intended to provide an update on the evolving therapeutic scenario of HER2-overexpressed BTC.
Methods:
We performed a systematic review of the literature to identify clinical trials investigating any regimen comprising a HER2-targeted therapy for metastatic BTC, and we conducted three subsequent meta-analyses on second-line phase II trials. The first one was performed to compare the group of HER2 3+ versus the group of HER2 2+ BTC patients for objective response rate (ORR). The second one compared patients according to the tumor location (gallbladder carcinoma [GBC] or extrahepatic cholangiocarcinoma [eCCA] versus intrahepatic cholangiocarcinoma [iCCA]) for ORR. The third one evaluated the overall outcomes in terms of overall survival (OS) and progression-free survival (PFS).
Results:
Patients with advanced BTC and HER2 3+ had better ORR compared to HER2 2+, with a 3.7-fold higher probability of experiencing objective responses (HR 3.70, 95% CI, 1.34-10.25, p = 0.0119). Likewise, patients with GBC or eCCA had a 2.74-fold higher probability of experiencing an objective response compared to patients with iCCA (HR 2.74, 95% CI, 1.12-6.73, p = 0.0275). The weighted pooled analysis of trials with anti-HER2 agents in second line or beyond revealed an mPFS of 4.9 months (95% CI, 4.2-5.6), while mOS was 10.8 months (95% CI, 9.0-12.8).
Conclusions:
Our meta-analyses have revealed improved efficacy in patients with HER2 3+ metastatic BTC and in patients with GBC or eCCA treated with anti-HER2 therapies, with a considerable mPFS and mOS in the overall population of the phase II trials analyzed. Further studies are paramount to confirm our preliminary results.
Insights
Targeted anti-HER2 therapies show improved outcomes for metastatic biliary tract cancers (BTC). Patients with HER2 3+ or gallbladder/extrahepatic cholangiocarcinoma (GBC/eCCA) experienced better response rates and survival.
Area of Science:
- Oncology
- Molecular Targeted Therapy
- Gastroenterology
Background:
- Metastatic biliary tract cancers (BTC) treatment has evolved with targeted therapies.
- Human epidermal growth factor receptor-2 (HER2) is a key molecular target in BTC.
- HER2-positive BTC presents a significant therapeutic challenge.
Purpose of the Study:
- To evaluate response rates and survival outcomes in HER2-positive metastatic BTC patients treated with anti-HER2 therapies.
- To compare efficacy based on HER2 expression levels (3+ vs. 2+).
- To analyze outcomes based on tumor location (GBC/eCCA vs. iCCA).
Main Methods:
- Systematic review and meta-analysis of phase II clinical trials.
- Comparison of objective response rate (ORR) between HER2 expression groups.
- Analysis of ORR based on tumor location.
- Evaluation of overall survival (OS) and progression-free survival (PFS).
Main Results:
- Patients with HER2 3+ BTC showed a 3.7-fold higher ORR than HER2 2+.
- Patients with GBC or eCCA had a 2.74-fold higher ORR compared to iCCA.
- Median PFS was 4.9 months and median OS was 10.8 months in the overall population.
Conclusions:
- Anti-HER2 therapies demonstrate improved efficacy in HER2 3+ metastatic BTC and in GBC/eCCA.
- Considerable median PFS and OS were observed in phase II trials.
- Further research is essential to validate these findings.
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