[3rd generation's TKI in lung cancer non-small cell EGFR-mutated having acquired a secondary T790M resistance]

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Activating EGFR mutations led to personalized medicine for EGFR-mutated non-small cell lung cancer (NSCLC) using first-generation TKIs.
• Tumor progression occurs within 10-16 months due to resistance mechanisms like the T790M mutation.
• Conventional treatments are limited for NSCLC patients with acquired resistance to EGFR-TKI therapy.

Purpose of the Study:

• To review novel third-generation TKIs (AZD9291 and rociletinib) for EGFR-mutated NSCLC.
• To highlight the effectiveness and clinical toxicities of these new molecules.
• To discuss their role in treating advanced NSCLC with T790M mutations.

Main Methods:

• Review of ongoing phase 1-3 clinical studies.
• Analysis of preliminary efficacy and toxicity data for AZD9291 and rociletinib.
• Focus on patients with acquired resistance and T790M mutations.

Main Results:

• Preliminary results indicate AZD9291 and rociletinib possess significant therapeutic properties.
• These third-generation TKIs demonstrate effectiveness in patients with T790M-mutated EGFR NSCLC.
• Clinical toxicity profiles are under evaluation in ongoing studies.

Conclusions:

• Third-generation TKIs represent a promising advancement in treating EGFR-mutated NSCLC with acquired resistance.
• AZD9291 and rociletinib offer potential new therapeutic options for patients harboring the T790M mutation.
• Further clinical evaluation is essential to establish their long-term efficacy and safety.