TTF1 was identified as a basic biomarker for Advanced Kras G12C-Mutated non-small cell lung cancer

Researchers at the University of Texas MD Anderson Cancer Center have identified a new biomarker, TTF-1, which predicted the survival results for patients with advanced Kras g12c-Non-Michocyte Lung Cancer (NSCLC), after treatment with KRAS targeted sotorasib treatment.

Results from the study, published today in Natural medicineThey found patients with pulmonary tumors expressing low TTF-1 levels that responded slightly to Sotorasib-with average survival without evolution (PFS) of 2.8 months and average total survival (OS) 4.5 months-while patients with tumors expressing high levels of TTF-1 had an average PFS of 8.1 months.

Since the TTF-1 test is usually performed in the diagnosis of lung cancer, it gives doctors an immediate tool to help detect patients who can benefit from Sotorasib and those who may need an alternative or intensive therapeutic approach. Our findings support the use of biomarkers to personalize care and could guide the exact implementation of strategies of combination with Kras inhibitors. “

Ferdinandos Skoulidis, MD, Ph.D., Head writer, Associate Professor of Thoracic/Head and Neck Medical Oncology

KRAS is the most common oncogenic driver in non -square NSCLC, found to be 25% to 30% of patients. Sotorasib is a targeted treatment designed to prevent the Kras G12C protein, which is about 13% of lung adenocarcinoma, the most common NSCLC type. Sotorasib was approved by the Food and Drug Administration in 2021 based on the results of the Codebreak 100 test. It was the first direct KRAS inhibitor to win regulations.

This study examined 317 patients with biological index with previous Advanced treatment Kras g12c-Mutant NSCLC involved in the Codebreak 200 clinical trial and 112 patients with organic index who were treated in the Codebreak 100 clinical trial.

In addition, the researchers found that the microenval of the tumor – the immune landscape around cancer cells – can also play a role in how well Sotorasib works. A subgroup of patients had “immune cold” tumors that had no expression of the PD-L1 immune protein immune sign, but better responded to Sotorasib rather than chemotherapy. These tumors are usually less likely to respond to immunotherapy.

“This finding is encouraging because it suggests that even patients who do not respond to immunotherapy may benefit from Sotorasib,” Skoulidis said. “It also opens the door to explore combined treatments, such as mating Sotorasib with chemotherapy to improve results for even more patients.”

The researchers were also able to prove that the rapid cleansing of the circulating tumor (CTDNA) – small fragments of DNA from the blood found in the blood – after the onset of Sotorasib was associated with much better results. Patients with detectable Kras g12c CTDNA during treatment had an increased risk of evolution compared to those with CTDNA clearance.

In some patients, CTDNA levels decreased only eight days in treatment, suggesting that a simple blood test could help doctors quickly determine who benefits from treatment.

This project significantly promotes precision medicine for patients with State G12C-NSCLC. Future studies will focus on further predicting the response to RAS inhibitors for patients with TTF-1 expressing tumors and identifying the most promising combination strategies for those who have a poor prognosis that lack TTF-1 expression.

Study restrictions included incomplete biomarker data for some patients, the possible period of data analysis and the size of the CTDNA table.

This study was funded by Amgen Inc.