Press Release
Sep 09, 2024
(San Diego, Calif.--September 9, 2024, 10:05 a.m. PCT) — The combination of osimertinib and savolitinib showed clinically meaningful improvement in objective response rate compared to osimertinib alone, according to research presented today at the International Association for the Study of Lung Cancer 2024 World Conference on Lung Cancer.
Approximately 20% to 30% of EGFRm NSCLC patients exhibit a primary unsatisfactory therapeutic effect to EGFR-TKIs therapy, according to Jin-Ji Yang, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital in Southern Medical University, China.
Professor Yang and his colleagues theorized that osimertinib, in combination with savolitinib, a selective MET inhibitor as first-line treatment, may improve efficacy and overcome MET-driven primary resistance in these patients.
The FLOWERS trial was established as a prospective, two-arm, randomized, multicenter study which enrolled 44 patients--23 were randomized to receive 80 mg qd of oral osimertinib alone (cohort 1) and 21 patients received 80 mg qd of osimertinib with 300 mg bid of savolitinib (cohort 2). Median follow up was 8.2 months, and the primary endpoint was objective response rate. The secondary endpoints included disease control rate, duration of response, progression-free survival, overall survival (OS), safety and tolerability.
MET overexpression is defined by IHC 3+ in ≥ 75% of tumor cells.
The criteria of MET amp are MET gene copy number (GCN) ≥5 and/or MET/CEP7
ratio ≥2 by tissue FISH or MET GCN≥5 by tissue NGS.
Professor Yang reported that the objective response rate in cohort 1 and cohort 2 were 60.9% (95%CI, 38.5-80.3%) and 90.5% (95% CI, 69.6-98.8%), respectively, with a disease control rate of 87% (95% CI, 66.4-97.2%) and 95.2% (95% CI,76.2-99.9%), respectively. The median duration of response was 8.4 months and 18.6 months, respectively, and is not yet mature.
“Osimertinib with savolitinib demonstrated a manageable safety profile, and with these results, has the potential to provide a novel first-line treatment option for patients who do not respond well to EGFR-TKIs therapy,” Professor Yang reported.
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About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.
About the WCLC:
The World Conference on Lung Cancer (WCLC) is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc2024.iaslc.org.
Sections:
Introduction:
Co-existing de novo MET amplification(amp) and/or overexpression (OE) was observed to have a shorter time to progression on EGFR-TKI monotherapy.. In the CTONG2008 (FLOWERS) study, we investigated the efficacy and safety of osimertinib monotherapy or osimertinib in combination with savolitinib as first-line therapy in pts with de novo MET amp and/or OE, EGFR -mutant, locally advanced or metastatic NSCLC.
Methods:
Results:
44 pts were enrolled and randomized. 23 and 21 pts received osimertinib monotherapy and osimertinib plus savolitinib, respectively. The median age was 58 years (range 29-74); 52.3% (23) pts were male. 86.4% (38) pts had ECOG PS of 1, and 34.1% (15) pts with brain metastases.
As of 28 May 2024, the median follow-up was 8.2 months. The confirmed ORR in cohort 1 and cohort 2 were 60.9% (95%CI, 38.5-80.3%) and 90.5% (95% CI, 69.6-98.8%), respectively, with DCR of 87% (95% CI, 66.4-97.2%) and 95.2% (95% CI,76.2-99.9%), respectively. The median DoR was 8.4 months and 18.6 months, respectively, and is not yet mature. The median PFS were 9.3 (95% CI, 7.4-NE) months and 19.6 (95% CI, 10.2-NE) months in the cohort 1 and cohort 2 with maturity of 34.8% and 23.8%, respectively. Treatment-related adverse events (TRAEs) were reported in 100% pts (44), of whom, 8.7% (2) pts reported grade ≥ 3 TRAEs in cohort 1 and 57.1% (12) in cohort 2. The most common TRAEs were diarrhea (56.5%), rash (52.2%), and pruritus (43.5%) in cohort 1, and rash (52.4%), thrombocytopenia (52.4%), and peripheral edema (42.9%) in cohort 2, mostly grade 1 or 2. No new safety signal and treatment-related death were observed.
Conclusions:
This is the first prospective, randomized study to explore the efficacy and safety of osimertinib with or without savolitinib in treatment naïve pts with EGFR m, MET -aberrant advanced NSCLC. Combination therapy with osimertinib and savolitinib showed clinically meaningful improvement in ORR with a manageable safety profile. It has the potential to provide a novel first-line treatment option for these patients.
Funding Source: AstraZeneca China
LBA Reason:
This is the first prospective study to report the efficacy and safety with combination of two oral drugs of osimertinib and savolitinib as 1st line therapy in EGFR mutant (EGFRm), advanced or metastatic non-small cell lung cancer (NSCLC) patients (pts) with de novo MET amplification(amp) and/or MET overexpression (OE). This combination may potentially delay resistance of osimertinib mediated by MET amp and/or OE with acceptable safety and may provide a new first-line treatment option for these patients. Since the time of primary analysis has not yet been reached, it will be reported in July 2024.
LBA Type of Analysis and Data:
From 26 h May 2022 to 28 h May 2024, a total of 44 pts were enrolled, 23 pts were randomly assigned to osimertinib monotherapy and 21 pts to osimertinib plus savolitinib. The demographics and baseline characteristics, the ORR as primary endpoint, DCR, DoR, preliminary PFS data, safety and tolerability data will be updated by July 2024 for this presentation, expecting ORR improvement will be observed in the cohort of combination therapy of osimertinib and savolitinib compared to the osimertinib monotherapy cohort.
Presenter:
Jin-Ji Yang, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, China
Presidential Symposium 2 (LIVESTREAMED)