Dacomitinib for the treatment of advanced or metastatic non-small-cell lung cancer

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Dacomitinib (PF-00299804) is a second-generation irreversible HER tyrosine kinase inhibitor (TKI).
• Preclinical studies showed dacomitinib's anti-tumor activity in lung cancer cell lines with sensitive and resistant EGFR mutations, including T790.
• Phase I studies established safety and tolerability, identifying stomatitis, diarrhea, and skin toxicities as dose-limiting toxicities with a maximum tolerated dose of 45 mg/day.

Purpose of the Study:

• To evaluate the anti-tumor activity and clinical efficacy of dacomitinib in lung cancer.
• To assess the safety and tolerability profile of dacomitinib.
• To explore dacomitinib's potential in both treatment-naive and previously treated non-small-cell lung cancer patients.

Main Methods:

• Preclinical evaluation in lung cancer cell lines with various EGFR mutations.
• Phase I clinical trials to determine safety, tolerability, and maximum tolerated dose.
• Phase II and III clinical trials to assess clinical activity in different patient populations.

Main Results:

• Dacomitinib demonstrated anti-tumor activity in preclinical lung cancer models with EGFR mutations.
• Phase I studies confirmed safety and tolerability, establishing the maximum tolerated dose.
• Phase II and III studies showed clinical activity in HER tyrosine kinase-naive and failure settings.

Conclusions:

• Dacomitinib exhibits promising anti-tumor activity and clinical efficacy in non-small-cell lung cancer.
• The drug is generally safe and well-tolerated, with identified dose-limiting toxicities.
• Further clinical trials are ongoing to fully elucidate dacomitinib's role in non-small-cell lung cancer treatment.