DIET & NUTRITION 
PATIENT EDUCATION 
OBESITY/WEIGHT MANAGEMENT 
EXERCISE/TRAINING 
LEGAL MATTERS 
GUIDELINES/RECOMMENDATIONS MET dysregulation can contribute to resistance after osimertinib in EGFR-mutated advanced NSCLC. SAFFRON randomized 324 patients with MET overexpression and/or amplification to osimertinib plus savolitinib or platinum–pemetrexed chemotherapy followed by pemetrexed maintenance. The combination improved independently reviewed progression-free survival and overall survival. These comparative phase 3 findings support biomarker-directed treatment investigation, but trial efficacy does not itself establish regulatory approval or guideline adoption.
Clinical Considerations
- Progression-free survival: Median PFS was 7.6 versus 5.4 months; HR 0.55 (95% CI, 0.42–0.72), favoring the oral combination.
- Overall survival: Median OS was 17.8 versus 12.9 months; HR 0.68 (95% CI, 0.50–0.91; P=.010).
- Response: Confirmed objective responses occurred in 51% versus 27%; median response duration was 9.7 versus 5.7 months.
- Safety: Grade ≥3 adverse events occurred in 64% versus 63%; peripheral edema was the combination’s most frequent treatment-related event.
- Applicability: Participants had ECOG performance status 0–1; stable CNS metastases were permitted. Findings do not establish benefit in poorer-performance populations.
- Testing limitations: The report omits MET assay thresholds; overexpression and amplification should not be treated as interchangeable findings.
Practice Applications
- Consider resistance profiling at progression when evaluating biomarker-directed treatment or trial eligibility, accounting for tissue availability and assay requirements.
- Review trial-defined MET eligibility before extrapolating results to an individual molecular report.
- Avoid equating oral administration or similar severe-event rates with lower toxicity, better quality of life, or equivalent safety.
- Evaluate current approval, guideline placement, and access before presenting this regimen as an available standard treatment.
