Dr Yang on Osimertinib Plus Savolitinib in MET-Aberrant, EGFR-Mutant Advanced NSCLC

“The overall response rate [with osimertinib plus savolitinib] was [over] 90%—a remarkable increase [compared with osimertinib alone].”

Jin-Ji Yang, MD, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, discusses findings from the phase 2 FLOWERS trial (NCT05163249) evaluating osimertinib (Tagrisso) in combination with savolitinib as a first-line treatment for patients with de novo MET-aberrant, EGFR-mutant advanced non–small cell lung cancer (NSCLC).

This open-label, randomized study enrolled treatment-naive patients with EGFR-mutant NSCLC harboring MET alterations to receive either osimertinib plus savolitinib (n = 21) or osimertinib monotherapy (n = 23). Findings demonstrated a statistically significant improvement in objective response rate (ORR) with the combination therapy compared with osimertinib alone, Yang begins. At the May 28, 2024, data cutoff and a median follow-up of 8.2 months, the ORR was 90.5% (95% CI, 69.6%-98.8%) in the combination arm vs 60.9% (95% CI, 38.5%-80.3%) in the monotherapy arm. The disease control rates were also 95.2% (95% CI, 76.2%-99.9%) vs 87.0% (95% CI, 66.4%-97.2%), respectively.

Additionally, although progression-free survival (PFS) data were immature, they suggested a potential clinical benefit with the combination regimen. The median PFS was 13.4 months (95% CI, 10.2-not evaluable [NE]) in the combination arm vs 9.5 months (95% CI, 7.4-NE) with osimertinib alone (HR, 0.80; 95% CI, 0.19-1.81).

Osimertinib plus savolitinib demonstrated a manageable safety profile consistent with prior studies. Any-grade treatment-emergent adverse effects (TEAEs) occurred in all patients in both arms. The rates of grade 3 or higher TEAES was 71.4% for the combination vs26.1% for osimertinib alone. TEAEs led to dose reduction in 23.8% of patients in the combination arm. No TEAEs led to death in any arm.