Recently approved drug effective against lung cancer caused by genetic mutations


A new study led by the University of Washington School of Medicine in St. Louis. Louis demonstrates that the new drug sotorasib benefits many patients with non-small cell lung cancer with a specific mutation in the KRAS gene. In a small subgroup of patients, the drug removed all evidence of tumors. The image on the left shows a scan showing a lung tumor (yellow circle) that has spread to the muscle. The image on the right shows the same patient after two months of sotorasib therapy. There is no visible tumor in the yellow circle on the right. Credit: Siddhartha Devarakonda

The new drug sotorasib reduces tumor size and demonstrates promises in improving survival among patients with lung tumors caused by a specific DNA mutation, according to the results of a global phase 2 clinical trial. is designed to stop the effects of the mutation, which is found in approximately 13% of patients with lung adenocarcinoma, a common type of non-small cell lung cancer.

The Food and Drug Administration approved sotorasib on May 28 as a specific therapy for patients with non-small cells cancer whose tumors express a specific mutation (called G12C) in the KRAS gene and which have undergone at least prior therapy for their cancer.

Non-small cell lung cancer accounts for more than 80% of all lung cancers. More than 200,000 new cases of non-small cell lung cancer are diagnosed each year in the United States.

The study, led by researchers at the University of Washington School of Medicine in St. Louis. Louis, the Perlmutter Cancer Center at NYU Langone Health in New York, the MD Anderson Cancer Center in Houston and the Memorial Sloan Kettering Cancer Center in New York, will perform on June 4 at the annual meeting of the American Society of Clinical Oncology and published the same day in The New England Journal of Medicine.

Sotorasib, also known as Lumakras, is manufactured by Amgen, who funded the trial.

“This is a group of patients whose tumors have been difficult to treat and for whom we had no specific therapies,” said Ramaswamy Govindan, co-senior author and medical oncologist, professor of medical oncology Anheuser Busch of the University of Washington. “The new drug is addressing an unmet need for these patients, targeting the most common mutation we can pursue. We are also continuing to research this drug in combination with other experimental drugs to see if we can further improve responses and survival. . “

The study involved 126 patients with non-small cell lung cancer who had a specific mutation in the KRAS gene. A single DNA error alters an important protein building block, placing a cysteine ​​where it should be a glycine. Tumors with the mutation make a version of the KRAS protein that is active almost constantly, driving tumor growth. Sotorasib, taken daily orally, blocks tumor growth by trapping the KRAS protein in its inactive form.

Most patients in the trial had been previously treated with standard chemotherapy along with an immunotherapy drug targeted at a protein called PD-1. To evaluate this new therapy, all patients enrolled in the study were treated with sotorasib; phase 2 trials evaluating safety and efficacy often do not include a placebo group.

The drug resulted in at least a reduction in tumor in 102 of 126 patients (82%). About 37% of patients ’tumors reduced their size by at least 30%. In contrast, response rates to standard therapy in these patients range from 6% to 20%.

The tumors of forty-two patients (34%) showed a partial response to therapy, meaning that the tumor was substantially reduced and its growth was controlled for a period of time; and four patients (3%) showed a complete response that left no evidence of disease. For tumors that shrunk, the it was reduced by about 60%, on average.

The effects of sotorasib lasted an average of 11 months, and the drug also showed progression-free survival, i.e. it did not continue to grow during this time, of nearly seven months. In contrast, patients with this lung cancer receiving standard therapy have an average progression-free survival of two to four months. The mean overall survival of all patients in the trial was 12 and a half months.

“We hope this approach will be a new option for lung cancer patients driven by this specific type of KRAS gene alteration,” said Govindan, who treats patients at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University. School of Medicine. “Alterations in the KRAS gene have long been considered unsuitable for specific therapies. There are numerous combined regimens being tested here at the Siteman Cancer Center and other leading cancer centers around the world. This puts the work that the University of Washington has excelled in the past several decades: studying the genomic alterations of tumors in order to identify the goals of treatment.This early research on the cancer genome is completely in circle to help our patients “.

Govindan and his team have led pioneering studies to define genomic alterations in lung cancer, including key contributions to The Cancer Genome Atlas, a national effort supported by the National Institutes of Health (NIH).

“The emotion surrounding this outcome of the trial is that sotorasib is now the first for lung cancer patients with KRAS mutations, “said author correspondent Vamsidhar Velcheti, MD, of NYU Langone Health.” KRAS-targeted treatments, decades in progress, are urgently needed for these patients with limited treatment options. “

Approximately 7% of patients discontinued treatment with sotorasib due to , but no life-threatening side effects and no patients died as a result of treatment. The drug caused adverse events severe enough to require a reduced dose of the drug in approximately 22% of patients. Nearly 70% of patients experienced drug-related side effects of some kind; the most common were diarrhea, fatigue, nausea, and increased liver enzyme levels, the latter an indicator of liver damage.

“Sotorasib showed a clinically significant benefit with no new safety issues in patients with this specific form of KRAS mutant lung cancer,” Govindan said. “Going forward, our team will try to report on the development of combined therapies with sotorasib and other emerging drugs, and determine which ones best fit the mixture of mutations in each patient. cells. “

Researchers are currently conducting a phase 3 clinical trial comparing the effectiveness of sotorasib with chemotherapy. called docetaxel in 345 which they do not have and this specific KRAS mutation.

FDA accepts first drug aimed at common lung cancer mutation

More information:
Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V, Govindan R. Sotorasib for lung cancers with KRAS mutations p.G12C (CodeBreak 100). The New England Journal of Medicine. June 4, 2021.

Citation: Recently Approved Effective Drug Against Genetic Mutation Lung Cancer (2021, June 4) Retrieved June 4, 2021 at -cancer.html

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