More potent treatment for a common cancer mutation provides hope
2 min read 29 August 2023
A tablet taken once a day could be a new treatment used to target one of the key drivers of cancer.
Research, published in this month’s New England Journal of Medicine, has shown that divarasib, a new targeted cancer treatment, is highly effective in treating patients with advanced or metastatic cancer linked to the KRAS G12C mutation.
Professor Jayesh Desai, Medical Oncologist, Associate Director of Clinical Research and Head Early Drug Development Trials at the Peter MacCallum Cancer Centre, said KRAS is a key protein that controls how cancer cells divide and survive.
“When the KRAS-G12C protein mutates it is always ‘switched on’ which means cells, including cancer cells, are more likely to divide uncontrollably leading to the development of tumours,” Professor Desai, the senior author on the paper, said.
“As world leaders in first in human trials, Peter Mac was heavily involved in the design and conduct of this global phase I trial which looked at the use of divarasib to treat patients with cancer linked to the KRAS G12C mutation.
“This first, large-scale trial involved patients from around the world with a variety of cancer types including non-small cell lung cancer and colorectal (bowel) cancer – two of Australia’s most deadly cancers.
“Patients on the trial had an impressive median progression free survival rate of more than 13 months for non-small cell lung cancer and almost 6 months for bowel cancer when treated with divarasib,” he said.
An illustration of the KRAS-G12C protein inside a cancer cell. Image: Dr Maja Divjak (Biomedical Animator - Peter Mac)
Professor Desai said previous in vitro studies have shown divarasib is fifty times more specific and twenty times more potent than other similar agents currently used to treat the KRAS mutation.
“Divarasib appears to demonstrate numerically higher response rates and improve progression free survival compared to existing single-agent KRAS G12C inhibitors,” he said.
“Based on these findings it is being evaluated further in clinical trials as a single agent and in combination with other treatments, across a number of cancer types.
“It has taken us years of research to build a more thorough understanding of how to target the KRAS mutation and to refine the science so we can develop molecules that are more even more potent.
“This once daily tablet treatment is true precision medicine specifically targeting the genetic mutation that is driving the cancer,” said Professor Desai.
Professor Desai explained that the trial enrolled 137 patients globally who had a variety of cancer types but most common were non-small cell lung cancer and colorectal (bowel) cancer.
Patients enrolled in the trial had to have disease that had progressed after at least one other treatment and where the best possible treatment for their disease was either not effective or not tolerated.
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