WILMINGTON, DE — AstraZeneca’s TAGRISSO combined with savolitinib extended median survival by nearly five months compared with chemotherapy in a Phase III trial involving patients with EGFR-mutated non-small cell lung cancer who developed resistance to earlier treatment, potentially establishing a new targeted therapy option for a difficult-to-treat patient population.
The SAFFRON trial found that the combination reduced the risk of death by 32% and the risk of disease progression or death by 45% compared with platinum-based chemotherapy, according to results presented at the European Society for Medical Oncology Congress 2026 in Madrid, Spain.
The findings were simultaneously published in The New England Journal of Medicine.
Patients receiving TAGRISSO, also known as osimertinib, plus savolitinib achieved median overall survival of 17.8 months, compared with 12.9 months among those receiving chemotherapy.
At one year, an estimated 70% of patients treated with the combination remained alive, compared with 53% in the chemotherapy group.
The overall survival hazard ratio was 0.68, with a 95% confidence interval of 0.50 to 0.91 and a p-value of 0.010, indicating a statistically significant reduction in mortality risk.
The trial enrolled patients whose EGFR-mutated non-small cell lung cancer had progressed following treatment with TAGRISSO and whose tumors exhibited high levels of MET protein expression or amplification of the MET gene.
MET-driven resistance is a recognized mechanism through which lung cancers can become less responsive to EGFR-targeted therapies.
The SAFFRON results suggest that continuing EGFR inhibition while adding treatment directed against MET may improve outcomes for patients whose disease has progressed through that resistance pathway.
Median progression-free survival reached 7.6 months with TAGRISSO plus savolitinib, compared with 5.4 months for patients receiving platinum-based chemotherapy.
The progression-free survival hazard ratio was 0.55, with a 95% confidence interval of 0.42 to 0.72 and a p-value below 0.001.
An estimated 36% of patients receiving the combination remained free of disease progression at one year, compared with 10% in the chemotherapy group.
The progression-free survival benefit was consistent across prespecified patient subgroups, including those with MET overexpression and those with MET amplification.
The results are significant for patients with EGFR-mutated non-small cell lung cancer, a form of the disease commonly treated with targeted therapies that inhibit abnormal EGFR signaling.
Although TAGRISSO can suppress EGFR-driven tumor growth, some cancers eventually develop alternative mechanisms that allow them to continue progressing despite treatment.
High levels of MET activity are associated with resistance in approximately one-third of patients whose EGFR-mutated lung cancer progresses after osimertinib treatment, according to the trial investigators.
Savolitinib is designed to inhibit MET signaling, while TAGRISSO continues targeting EGFR. The combination offers an oral treatment approach intended to address both pathways without relying on intravenous chemotherapy.
Professor Shun Lu, director of the Shanghai Lung Cancer Center at Shanghai Chest Hospital and principal investigator of SAFFRON, emphasized the importance of identifying the biological mechanism responsible for treatment resistance.
“These results have the potential to establish a new global standard of care for the third of patients with EGFR-mutated non-small cell lung cancer experiencing high levels of MET-driven resistance after osimertinib,” Lu stated.
He also identified MET testing as an important consideration in determining which patients could benefit from the combination.
The trial represents the first global Phase III study to demonstrate statistically significant improvements in both progression-free and overall survival with this treatment approach in patients with MET-driven resistance following TAGRISSO.
Savolitinib is being developed through a partnership involving AstraZeneca and HUTCHMED, whose acting chief executive officer and chief financial officer, Johnny Cheng, characterized the findings as progress toward addressing resistance to EGFR-targeted treatment.
Susan Galbraith, AstraZeneca’s executive vice president of oncology and hematology research and development, indicated that maintaining EGFR inhibition while targeting MET could provide a treatment strategy for patients whose cancers have progressed despite earlier targeted therapy.
The results support the potential use of TAGRISSO plus savolitinib as a biomarker-directed, all-oral treatment option in this setting.
Any broader clinical use of the combination in this treatment setting would depend on applicable regulatory authorization.
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