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SAN DIEGO — Mixture remedy with osimertinib and savolitinib may change into a novel first-line remedy possibility for sufferers with de novo MET-aberrant, EGFR-mutated superior non–small cell lung most cancers (NSCLC), in keeping with outcomes of the part 2 FLOWERS research.
In contrast with EGFR inhibitor osimertinib alone, the mix demonstrated a clinically significant enchancment within the goal response price — the research’s main endpoint — with a optimistic development in progression-free survival and a manageable security profile.
About 30% sufferers with EGFR-mutated NSCLC fail to reply effectively to EGFR-tyrosine kinase inhibitors (TKIs), defined Jin-Ji Yang, MD, with Guangdong Lung Most cancers Institute, Guangzhou, China, who reported the research outcomes on the World Conference on Lung Cancer (WCLC) 2024.
Knowledge instructed that de novo MET amplification happens in as much as 5% sufferers with treatment-naive EGFR-mutated superior NSCLC, and MET overexpression happens in as much as 15% these sufferers.
Coexistence of EGFR mutation and MET amplification/overexpression reduces sensitivity to EGFR-TKI remedy “and is probably going the mechanism for mediating main resistance to first-line EGFR-TKI monotherapy,” Yang defined in her presentation.
Osimertinib is a third-generation EGFR-TKI recommended because the first-line remedy for EGFR-mutant superior NSCLC. Savolitinib is a extremely selective MET-TKI which has demonstrated antitumor exercise in numerous cancers with MET alterations.
The FLOWERS research is the primary to check whether or not combining the 2 brokers may enhance efficacy and overcome MET-driven main resistance in these sufferers.
The part 2 research enrolled 44 treatment-naive sufferers with de novo MET-aberrant, EGFR-mutant, stage IIIB-IV NSCLC; 23 had been randomly allotted to obtain oral osimertinib (80 mg as soon as every day) alone and 21 to obtain oral osimertinib (80 mg as soon as every day) plus savolitinib (300 mg twice every day).
At a median follow-up of 8.2 months, the target response price was 60.9% with osimertinib monotherapy vs 90.5% with mixture remedy. The illness management price was additionally higher with the mix remedy than with monotherapy (95.2% vs 87%).
Median length of response (not but mature) was 8.4 months with monotherapy vs 18.6 months with mixture remedy.
Preliminary progression-free survival information additionally confirmed a development in favor of mixture remedy over monotherapy (a median of 19.3 vs 9.3 months; hazard ratio, 0.59).
Most treatment-related antagonistic occasions had been grade 1 or 2, and there have been no deadly antagonistic occasions.
Therapy-related antagonistic occasions of grade 3 or greater had been extra widespread with mixture remedy (57.1% vs 8.7%). The commonest occasions with monotherapy had been diarrhea (56.5%), rash (52.2%), and pruritus (43.5%) and with twin remedy had been rash (52.4%), thrombocytopenia (52.4%), and peripheral edema (42.9%).
The outcomes confirmed that the mix remedy has the potential to change into a first-line remedy possibility for sufferers who don’t reply effectively to EGFR-TKIs alone, mentioned Yang, in a press launch.
Discussant for the research Paul Paik, MD, thoracic oncologist at Memorial Sloan Kettering Most cancers Heart in New York Metropolis, mentioned this research “provides to information suggesting excessive MET expression is perhaps a poor prognostic or predictive marker, the outcomes of that are improved with MET inhibition.”
He cautioned, nevertheless, that there seems to be “high quality of life, side-effect trade-offs with twin MET plus EGFR TKI upfront.”
Paik mentioned he appears ahead to outcomes from FLOWERS on serial circulating tumor DNA and formal androgen receptor testing, which “may support in additional assessing clonality and characterizing MET as a co-driver on this setting.”
The research was funded by AstraZeneca China. Yang had no disclosures. Paik disclosed relationships with EMD Serono, Bicara, Novartis, and Summit.
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