HER2/neu may not be an interesting target in biliary cancers: results of an early phase II study with lapatinib
Joshua Peck1, Lai Wei, Mark Zalupski
1The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, Ohio, USA.
Purpose:
Biliary cancers (BCs) respond poorly to chemotherapy. Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and HER2/neu, both implicated in cholangiocarcinogenesis. This trial was designed to determine the safety and efficacy of lapatinib in BC.
Methods:
A Fleming phase II design with a single stage of 25 patients was used. The dose of lapatinib was 1,500 mg/day administered orally in 28-day cycles. Tumor and blood specimens were analyzed for expression of HER2/neu and EGFR.
Results:
Nine patients with BC enrolled in this study. The study was terminated early because of futility. The most common toxicities were nausea and fatigue (78%) and diarrhea (67%). No responses were observed. Of 8 evaluable patients, 4 (50%) had stable disease. Median progression-free survival was 2.6 months (95% CI 1.6-4.4) and median overall survival was 5.1 months (95% CI 2.0-16.5). No somatic mutations in EGFR (exons 18-21) or HER2/neu were found. We did not find evidence of HER2 overexpression.
Conclusions:
Lapatinib is well tolerated but failed to show activity as a single agent in treating patients with BC. Despite the small patient population, our study is consistent with previous findings, suggesting that targeting HER2/neu does not appear to be an effective therapy for BC.
Insights
Lapatinib, a targeted therapy for biliary cancers (BCs), was well-tolerated but showed no significant efficacy. This study suggests that targeting HER2/neu is not an effective treatment strategy for BC.
Area of Science:
- Oncology
- Cancer Research
- Pharmacology
Background:
- Biliary cancers (BCs) exhibit poor response to conventional chemotherapy.
- Epidermal growth factor receptor (EGFR) and HER2/neu are implicated in cholangiocarcinogenesis.
Purpose of the Study:
- To evaluate the safety and efficacy of lapatinib, a dual EGFR and HER2/neu inhibitor, in patients with biliary cancers.
- To determine the potential of lapatinib as a targeted therapy for BC.
Main Methods:
- A Fleming phase II clinical trial design was employed.
- Twenty-five patients were planned, with lapatinib administered orally at 1,500 mg/day in 28-day cycles.
- Tumor and blood samples were analyzed for EGFR and HER2/neu expression.
Main Results:
- The study enrolled nine patients and was terminated early due to futility.
- Common toxicities included nausea, fatigue, and diarrhea; no objective responses were observed.
- Median progression-free survival was 2.6 months and median overall survival was 5.1 months. No EGFR or HER2/neu mutations or HER2 overexpression were detected.
Conclusions:
- Lapatinib was well-tolerated in patients with BC but demonstrated no significant anti-cancer activity as a single agent.
- Targeting HER2/neu does not appear to be an effective therapeutic approach for biliary cancers.
- Findings are consistent with previous research, reinforcing the limited role of HER2-targeted therapy in BC.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:38Mitogens and the Cell Cycle