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A daily pill can double survival time in patients with the world’s deadliest cancer, according to the results of a clinical trial that experts are saying is a “gamechanger” and one of the biggest breakthroughs in decades.
Currently, there are few treatments for pancreatic cancer, and most do little or nothing to help. For decades, scientists have worked relentlessly trying to find clever solutions for a form of cancer that is often found late. More than half of patients are only diagnosed after it has spread.
Now experts at the world’s largest cancer conference are hailing the arrival of a smart drug called daraxonrasib, which they say could pave the way for a treatment revolution.
In the trial of 500 patients, all of whom had pancreatic cancer that had spread, the pill doubled survival time, with fewer side-effects compared with chemotherapy. The findings were presented at the American Society of Clinical Oncology’s (Asco) annual meeting in Chicago.
Patients who took the drug lived substantially longer, for an average of 13.2 months, compared with 6.6 to 6.7 months for patients who had chemotherapy, the trial found.
“These results are landscape-changing,” said Dr Rachna Shroff, the chief of oncology at the University of Arizona Cancer Center and an Asco expert in gastrointestinal cancers, who was not involved with the study. “We are seeing unprecedented survival.”
When Shroff first read the results of the trial, led by researchers at the world-renowned Dana-Farber Cancer Institute in Boston, she wept, she said.
“Having treated pancreatic cancer for 16 years, I actually started crying in clinic. This is such an incredibly impactful study for our patients, and I really congratulate the [trial] investigators.”
Dr Julie Gralow, Asco’s chief medical officer and executive vice-president, who was also not involved with the trial, said it was a “gamechanger”. She added: “I’ve heard this study described as a home run. I would actually say it’s a grand slam.”
Daraxonrasib works by targeting a protein, Kras, that fuels nearly all pancreatic cancers. The drug glues molecules together to grab and shut down Kras.
Kras is part of the Ras family of genes. They can cause cancer cells to keep receiving signals to grow and divide, even when they should not. This can lead to cancer growing and spreading.
More than 90% of patients with the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (mPDAC), have a mutation in the Kras gene. This is called a Ras G12 variant, and results in an overactive Kras protein.
Daraxonrasib is a new kind of Ras inhibitor called a Ras(On) multi-selective inhibitor. It can turn off the Kras protein to stop cancer growth whether there is a Kras variant or not, and regardless of which variant it is.
“The idea of targeting Kras has always been the holy grail in most malignancies, but specifically in pancreas cancer, because it is nearly ubiquitous and it is an early driver of pancreas cancer growth,” said Shroff.
“The Ras revolution is here, and this study is proof of principle that targeting Kras in pancreatic cancer is feasible and effective.”
Paula Hanford, the chief executive of UK-based Pancreatic Cancer Action, said the discovery was one of the most significant developments in treatment that she had ever seen.
“For far too long, people diagnosed with pancreatic cancer have had incredibly limited treatment options and survival rates that have remained devastatingly low. To see a trial showing the potential to nearly double survival time in advanced pancreatic cancer is hugely encouraging and gives real hope to patients and families facing this disease.”
Anna Jewell, the director of services, research and innovation at Pancreatic Cancer UK, said the results were “exciting”.
“By blocking the activity of Kras mutations, this drug, daraxonrasib, has been shown to improve survival in people with advanced pancreatic cancer. Patients were given months more precious time with their loved ones.”
But the next step will be ensuring that these types of drugs are made available to patients, she said. “Tragically, half of all people with pancreatic cancer die within just three months of their diagnosis.
“More time with those we love most is truly priceless. We must do everything possible to ensure the most promising new treatments are available.”
Experts in Chicago also told the Guardian that because Ras genes fuelled other cancers, there was hope of breakthroughs elsewhere. Similar drugs were being tested for lung and colon cancers, they said.
