A NEW targeted drug combination significantly improved progression-free and overall survival compared to chemotherapy for patients with resistant lung cancer, according the results from a Phase III trial presented at the European Society of Medical Oncology (ESMO) Congress.
Osimertinib plus savolitinib reduced the risk of death by 32% compared with platinum–pemetrexed chemotherapy in patients with a molecularly defined form of advanced lung cancer, according to Phase III SAFFRON trial results.
The global, randomised study evaluated the oral combination in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) with MET overexpression and/or amplification following previous osimertinib treatment.
Targeted treatment options remain limited for patients with these specific mutations, despite that non-small cell lung cancer is the most common type of cancer globally. .
Osimertinib, a tyrosine kinase inhibitor (TKI) targets epidermal growth factor receptors (EGFR), while savolitinib selectively inhibits MET.
Earlier findings from the Phase II SAVANNAH study demonstrated clinically meaningful response rates with the combination, supporting its evaluation against chemotherapy.
SAFFRON enrolled 338 adults whose disease had progressed following first- or second-line osimertinib. Eligibility required specified EGFR mutations alongside high MET protein expression and/or MET gene amplification, assessed through tumour testing.
Participants were randomly assigned to receive osimertinib 80 mg once daily plus savolitinib 300 mg twice daily, or platinum-pemetrexed chemotherapy.
Chemotherapy comprised pemetrexed with carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance pemetrexed.
The combination group included 171 patients, while 167 received chemotherapy. The primary endpoint was progression-free survival assessed by blinded independent central review.
Other endpoints included overall survival, investigator-assessed progression-free survival, and safety.
At the data cut-off of 6 July 2026, median progression-free survival was 7.6 months with osimertinib plus savolitinib, compared with 5.4 months with chemotherapy.
The combination reduced the risk of disease progression or death by 45% (HR: 0.55; 95% CI: 0.42–0.72; p<0.001). The progression-free survival benefit was consistent across the MET-overexpressed and MET-amplified subgroups.
Median overall survival reached 17.8 months with the targeted combination versus 12.9 months with chemotherapy, corresponding to a 32% reduction in the risk of death (HR: 0.68; 95% CI: 0.50–0.91; p=0.010).
Median duration of response, assessed by blinded independent central review, was also longer with the combination, at 9.7 months versus 5.7 months.
Treatment-emergent adverse events of any cause occurred in 99% of patients receiving osimertinib plus savolitinib and 97% receiving chemotherapy. Grade 3 or higher events occurred in 64% and 63%, respectively.
Serious treatment-emergent adverse events were more frequent with the combination, occurring in 41% versus 28%. Treatment-emergent adverse events led to treatment discontinuation in 14% versus 8%.
However, Grade 3 or higher treatment-related adverse events occurred less frequently with the combination than with chemotherapy, at 40% versus 52%.
The investigators concluded that osimertinib plus savolitinib provided statistically significant and clinically meaningful survival improvements with a manageable safety profile.
The findings, which were labelled “practice changing” by researchers, support the oral combination as an effective targeted treatment option for this selected population following osimertinib.
Reference
Lu S et al. Osimertinib (osi) + savolitinib (savo) vs platinum–pemetrexed (plat–pem) in EGFRm MET-overexpressed (OE) and/or -amplified (AMP) advanced NSCLC post-osi: SAFFRON phase (Ph) 3 primary results. Abstract LBA6. ESMO Congress 2026. Clinical trial: NCT05261399. ESMO Congress, 23-27 October 2026.
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