The following is the summary of “Design and Rationale for a Phase II, Randomized, Open-Label, Two-Cohort Multicenter Interventional Study of Osimertinib with or Without Savolitinib in De Novo MET Aberrant, EGFR-Mutant Patients with Advanced Non-Small-Cell Lung Cancer: The FLOWERS Trial” published in the January 2023 issue of Clinical Lung Cancer by Chen, et al.

Common genetic abnormalities in advanced Non-Small-Cell Lung CancerNSCLC include epidermal growth factor receptor (EGFR) mutations, which are linked to impressive survival gains from first-line treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). On the other hand, about 30% of individuals develop primary resistance to EGFR-TKIs. Time to progression on EGFR-TKI monotherapy is shorter in patients with coexisting MET amplification/over-expression. Patients with EGFR-mutant advanced NSCLC are candidates for first-line treatment with osimertinib (TAGRISSO, AZD9291). The MET-TKI savolitinib (AZD6094, HMPL-504) has shown anti-tumor effectiveness in various malignancies where MET has been altered.

The purpose of the FLOWERS study was to compare the efficacy and safety of osimertinib plus or minus savolitinib as first-line therapy for patients with de novo MET amplification/overexpression, EGFR mutation positivity, and locally or distantly progressed or metastatic NSCLC. About 44 patients will be randomly assigned to receive either osimertinib (80 mg once daily) monotherapy or osimertinib (80 mg once daily) and savolitinib (300 mg twice daily) combination therapy; patients in the osimertinib monotherapy cohort confirmed as MET positive (MET-amplified/over-expressed) after disease progression will have the opportunity to receive the cross-over combination therapy as second-line treatment. The objective response rate will serve as the primary metric. 

Progression-free survival, response length, disease control rate, overall survival, safety, and tolerability will be important secondary goals. Patients with de novo MET-amplified/over-expressed, EGFR-mutant positive, treatment-naive, advanced NSCLC will benefit from the study’s findings because they will provide meaningful guidance in clinical practice based on new information about the efficacy and safety of EGFR-TKI plus MET-TKI combination therapy (osimertinib plus savolitinib) (NCT05163249).