When EGFR meets MET: Dual blockade as the next post-TKI standard?

Area of Science:

• Oncology
• Medical Research
• Clinical Trials

Background:

• Non-small-cell lung cancer (NSCLC) with EGFR mutations and MET amplification presents a treatment challenge after EGFR tyrosine kinase inhibitor (TKI) failure.
• Current treatment options for this patient subgroup are limited, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

• To evaluate the efficacy of combining savolitinib with osimertinib compared to chemotherapy in patients with EGFR-mutated, MET-amplified NSCLC following prior EGFR TKI treatment.
• To establish the first Phase 3 evidence for dual EGFR and MET inhibition in this specific NSCLC population.

Main Methods:

• The SACHI trial was a Phase 3 study comparing savolitinib plus osimertinib against chemotherapy.
• Progression-free survival (PFS) was the primary endpoint, with secondary endpoints including overall survival and objective response rate.

Main Results:

• Savolitinib plus osimertinib demonstrated a significant improvement in PFS, nearly doubling it compared to chemotherapy (9.8 months vs. 5.4 months).
• The hazard ratio for progression was 0.34, indicating a substantial reduction in the risk of disease progression with the combination therapy.

Conclusions:

• Dual inhibition of EGFR and MET with savolitinib and osimertinib is a highly effective strategy for patients with EGFR-mutated, MET-amplified NSCLC after EGFR TKI failure.
• This represents a significant advancement in targeted therapy for NSCLC, offering a new treatment paradigm for a difficult-to-treat patient group.