New developments in the management of non-small-cell lung cancer, focus on rociletinib: what went wrong?

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• The evolution of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is crucial for targeted cancer therapy.
• Resistance to earlier generations of EGFR-TKIs necessitated the development of third-generation inhibitors.
• Rociletinib, a third-generation EGFR-TKI, faced development challenges, prompting a review of its trajectory.

Approach:

• Comprehensive review of the historical development and advancements in EGFR-TKIs.
• Detailed analysis of rociletinib's development, clinical trials (TIGER trials), and reasons for its discontinuation.
• Comparative efficacy assessment of rociletinib and osimertinib against various EGFR mutations and resistance mechanisms.

Key Points:

• Discusses the impact of diverse oncogenic mutations on EGFR activity and their implications for TKI efficacy.
• Compares the clinical trial outcomes and resistance profiles of rociletinib and osimertinib.
• Highlights the specific challenges and factors contributing to the cessation of rociletinib's development.

Conclusions:

• The review provides insights into the complexities of EGFR-TKI development, particularly concerning rociletinib.
• Understanding resistance mechanisms and comparative efficacy is vital for future EGFR-TKI drug discovery.
• Lessons learned from rociletinib's development can inform the future landscape of targeted cancer therapies.