[Osimertinib (Tagrisso^®): Activity, indication and modality of use in non-small cell lung cancer]

Area of Science:

• Oncology
• Pharmacology

Background:

• Acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in advanced EGFR-mutated non-small cell lung cancer (NSCLC) often involves the T790M mutation.
• This mutation occurs in approximately 50% of cases of secondary resistance to first-line EGFR TKI treatment.

Purpose of the Study:

• To evaluate the efficacy and safety of osimertinib, a third-generation EGFR TKI, in patients with advanced EGFR-mutated NSCLC who have developed resistance to prior EGFR TKI therapy.
• To assess the utility of detecting the T790M mutation in circulating tumor DNA (ctDNA) for treatment selection.

Main Methods:

• Phase I and II clinical trials were conducted to assess osimertinib's efficacy and safety.
• Patient populations included those with advanced EGFR-mutated NSCLC progressing on first-generation EGFR TKI.
• T790M mutation status was assessed, including screening via plasma ctDNA.

Main Results:

• Osimertinib demonstrated a response rate of 51% in a phase I trial, increasing to 61% in patients with the T790M mutation.
• Progression-free survival was 9.6 months in patients with the T790M mutation.
• The toxicity profile was acceptable, with common side effects including diarrhea and rash.
• Preliminary phase II data corroborated these findings.
• Plasma ctDNA screening for the T790M mutation showed good diagnostic performance.

Conclusions:

• Osimertinib is an effective treatment option for advanced EGFR-mutated NSCLC harboring the T790M resistance mutation.
• Plasma-based T790M mutation screening is a viable diagnostic approach.
• Osimertinib offers a favorable efficacy and safety profile in this patient population.