Researchers from The College of Texas MD Anderson Most cancers Middle have recognized a brand new biomarker, TTF-1, that was predictive of survival outcomes for sufferers with superior KRAS G12C-mutated non-small cell lung most cancers (NSCLC), following therapy with the KRAS focused remedy sotorasib.
Outcomes from the research, printed in Nature Drugs, discovered sufferers with lung tumors that categorical low TTF-1 ranges responded poorly to sotorasib—with a median development free survival (PFS) of two.8 months and a median general survival (OS) of 4.5 months—whereas sufferers with tumors expressing excessive TTF-1 ranges had a median PFS of 8.1 months and a median OS of 16 months.
“Since TTF-1 testing is routinely carried out in lung most cancers analysis, it provides physicians a direct device to assist establish these sufferers who might profit from sotorasib and those that may have another or intensified therapy method,” mentioned lead creator Ferdinandos Skoulidis, M.D., Ph.D., affiliate professor of Thoracic/Head and Neck Medical Oncology.
“Our findings help using biomarkers to personalize care and will information the exact utility of mixture methods with KRAS inhibitors.”
KRAS is the most typical oncogenic driver in non-squamous NSCLC, discovered to be mutated in 25% to 30% of sufferers. Sotorasib is a focused remedy designed to dam the KRAS G12C mutant protein, which is present in roughly 13% of lung adenocarcinomas, the most typical sort of NSCLC.
Sotorasib was permitted by the Meals and Drug Administration in 2021 based mostly on outcomes from the CodeBreaK 100 trial. It was the primary direct KRAS inhibitor to earn regulatory approval.
This research checked out 317 biomarker-evaluable sufferers with beforehand handled superior KRAS G12C-mutated NSCLC who had been concerned within the CodeBreaK 200 scientific trial and 112 biomarker-evaluable sufferers handled within the CodeBreaK 100 scientific trial.
As well as, researchers discovered that the tumor microenvironment—the immune panorama surrounding most cancers cells—can also play a task in how properly sotorasib works. One subgroup of sufferers had “immune chilly” tumors that lacked expression of the immune checkpoint protein PD-L1, however they responded higher to sotorasib than to chemotherapy. These tumors are usually much less seemingly to reply to immunotherapy.
“This discovering is encouraging as a result of it means that even sufferers who do not reply to immunotherapy would possibly nonetheless profit from sotorasib,” Skoulidis mentioned. “It additionally opens the door to exploring mixture remedies, like pairing sotorasib with chemotherapy to enhance outcomes for much more sufferers.”
Researchers had been additionally capable of show that fast clearance of circulating tumor DNA (ctDNA)—small fragments of DNA from the tumor discovered within the blood—following initiation of sotorasib was linked with significantly better outcomes. Sufferers with detectable KRAS G12C ctDNA throughout therapy had an elevated danger of development in comparison with these with ctDNA clearance.
In some sufferers, ctDNA ranges dropped as quickly as eight days into therapy, suggesting {that a} easy blood take a look at might assist medical doctors shortly establish who’s benefiting from the remedy.
This work considerably advances precision drugs for sufferers with KRAS G12C-mutant NSCLC. Future research will concentrate on additional refining response prediction to RAS inhibitors for sufferers with TTF-1 expressing tumors and on figuring out probably the most promising mixture methods for these with a poor prognosis who lack TTF-1 expression.
Limitations of the research included incomplete biomarker knowledge for some sufferers, the potential timing of the info evaluation, and the ctDNA panel measurement.
Extra data:
Ferdinandos Skoulidis et al, Molecular determinants of sotorasib scientific efficacy in KRASG12C-mutated non-small-cell lung most cancers, Nature Drugs (2025). DOI: 10.1038/s41591-025-03732-5
Quotation:
New biomarker might information finest use of KRAS inhibitors in lung most cancers (2025, Could 28)
retrieved 28 Could 2025
from https://medicalxpress.com/information/2025-05-biomarker-kras-inhibitors-lung-cancer.html
This doc is topic to copyright. Other than any truthful dealing for the aim of personal research or analysis, no
half could also be reproduced with out the written permission. The content material is offered for data functions solely.
