A combination of two drugs to treat mutant versions of the ‘death star’, as the KRAS gene is known, whose protein causes one in four cancers, has shown promise in treating tumors in patients with advanced cancer of the thyroid, ovary and lung.
The trial that has reached this conclusion has been carried out in 30 patients with a variety of mutations in the KRAS gene, to whom the drugs VS-6766 and everolimus have been administered. The results obtained have been announced at the annual meeting of the American Society of Clinical Oncology (ASCO) to be held in 2022.
Previous studies of similar drugs were unsuccessful because they caused serious side effects in patients. Now, they have achieved better results thanks to an innovative dosing schedule that limits their toxicity, giving participants the two drugs twice a week for a period of three weeks, followed by a week off.
The results showed that with this administration pattern of the drug combination, tumors were reduced by more than 30% in two of the 11 patients with lung cancer and tumor growth was controlled in the remaining nine. The participants already had a history of cancer treatments, such as chemotherapy or next-generation immunotherapy, but they stopped responding when adapting to the treatment, in addition to showing drug resistance.
Treatment option for many more people with cancer
It is estimated that 40% of lung cancers, 45% of bowel cancers and 90% of pancreatic cancers are caused by mutant versions of KRAS, which until recently were difficult to detect. However, in 2021 the first effective drug was approved in the United States, but it only targets the G12C variant, a mutation that only 40% of lung cancer patients have, so most cannot benefit from this drug. .
The combination of drugs reduced tumors by 30% in 2 of the 11 patients with lung cancer and controlled tumor growth in the remaining 9
The new combination of drugs makes the KRAS or ‘death star’ gene less effective, since it simultaneously blocks the two pathways on which it relies to achieve its growth. Therefore, these two drugs could attack cancers caused by other KRAS mutations, which means that many more people could qualify for improvement thanks to them.
“Our early-stage study shows that an innovative combination of drugs can effectively target multiple mutant versions of KRAS, which is one of the most dangerous mutations in cancer and one of the most difficult to create treatments for. This could represent a new treatment paradigm targeting KRAS mutations in multiple tumor types, including low-grade serous ovarian and lung cancer,” said Udai Banerji, Director of Drug Development at the Cancer Research Institute. from London (UK).
Dr. Anna Minchom, Drug Development Team Leader, concludes: “It is fantastic to see that this innovative drug combination is showing potential to treat patients with a variety of cancer types, who have been left without other treatment options. . Patients with KRAS-mutated non-small cell lung cancer, other than those with a subtype known as KRAS G12C, currently have no specific treatment options.”
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