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Published on: September 25, 2018
The prospect of patritumab for treating non-small cell lung cancer
1a Department of Thoracic Oncology , National Cancer Center Hospital , Tokyo , Japan.
Introduction:
The mutation or expression of HER family members serves as a therapeutic target for tyrosine kinase inhibitors or monoclonal antibodies in diverse cancers, such as non-small cell lung cancer, breast cancer, gastric cancer, head and neck cancer, colorectal cancer, pancreatic cancer and glioblastoma. HER3, which heterodimerizes with HER1 and HER2, has received much attention as a potential target for anti-EGFR treatment. Patritumab is a novel, fully human monoclonal antibody directed against HER3. Areas covered: In this review article, an overview of the market, chemistry, pharmacodynamics, pharmacokinetics, efficacy, and safety of patritumab is provided based on data from phase I studies, a combination phase I trial, and a randomized phase II trial comparing two doses of patritumab. Expert opinion: The combination of patritumab plus erlotinib has shown a promising efficacy and safety in early-phase clinical trials. In a randomized phase II trial, higher mRNA expression of heregulin (a ligand of HER3) was associated with better progression-free survival and a tendency toward improved overall survival. In the era of precise treatment based on an appropriate target with a predictive biomarker, further studies with patritumab are needed to realize its potential in cancer treatment.
Insights
Patritumab, a HER3-targeted antibody, shows promising efficacy and safety when combined with erlotinib in early cancer trials. Higher heregulin expression correlated with better progression-free survival, highlighting its potential in precision medicine.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- HER family mutations are key targets for cancer therapies like tyrosine kinase inhibitors and monoclonal antibodies.
- HER3, a heterodimer with HER1 and HER2, is a significant target for anti-EGFR treatments.
- Patritumab is a novel monoclonal antibody specifically targeting HER3.
Purpose of the Study:
- To provide a comprehensive overview of patritumab, including its market, chemistry, pharmacodynamics, pharmacokinetics, efficacy, and safety.
- To evaluate the efficacy and safety of patritumab in combination with erlotinib.
- To explore the correlation between heregulin (HER3 ligand) expression and patient outcomes.
Main Methods:
- Review of data from phase I studies, a combination phase I trial, and a randomized phase II trial.
- Assessment of patritumab's efficacy and safety profiles.
- Analysis of mRNA expression of heregulin as a predictive biomarker.
Main Results:
- The combination of patritumab and erlotinib demonstrated promising efficacy and safety in early-phase clinical trials.
- Higher mRNA expression of heregulin was associated with improved progression-free survival in a phase II trial.
- A trend towards improved overall survival was observed in patients with higher heregulin expression.
Conclusions:
- Patritumab, in combination with erlotinib, presents a promising therapeutic option for various cancers.
- Heregulin mRNA expression may serve as a predictive biomarker for patritumab treatment efficacy.
- Further research is essential to fully realize patritumab's potential in precision cancer therapy.
